MODEL9089538076
type: SBMLModel
species: 419666
species: 418846
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species: 422265
units def: 443280
species: 418866
species: 421966
species: 419826
reaction: 423925
reaction: 426425
species: 422086
reaction: 423445
species: 419846
reaction: 425025
reaction: 422765
species: 421346
reaction: 425145
species: 419726
species: 420786
species: 421546
reaction: 425705
species: 420466
species: 419566
species: 418786
species: 420666
species: 422246
species: 419026
species: 420506
reaction: 422665
species: 420166
reaction: 425485
reaction: 423385
species: 421186
reaction: 424005
reaction: 424765
species: 420186
reaction: 426105
reaction: 422985
species: 419486
reaction: 424485
species: 421206
reaction: 425365
species: 420366
reaction: 422465
reaction: 423126
reaction: 425925
reaction: 425865
species: 419366
species: 420566
reaction: 425285
reaction: 426205
species: 418946
species: 421486
reaction: 423865
reaction: 424585
reaction: 426325
reaction: 424845
species: 418486
species: 420686
species: 420886
reaction: 424405
reaction: 422386
reaction: 423325
reaction: 422405
reaction: 423085
reaction: 422685
species: 422126
reaction: 424425
reaction: 423065
reaction: 426165
species: 419466
species: 420946
reaction: 426125
reaction: 423185
reaction: 422566
reaction: 425905
reaction: 425565
reaction: 422725
reaction: 423685

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type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.1
initial amount: NaN
in compartment: 418386

418386
type: Compartment
constant: true
size: 1.5E-15
spatial dimensions: 3.0

418846
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
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421906
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

422265
type: Species
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

443316
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND

443304
type: SBMLUnit
exponent: -1.0
scale: -6
multipler: 1.0
kind: MOLE

443292
type: SBMLUnit
exponent: 2.0
scale: 0
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418866
type: Species
constant: false
boundary condition: false
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initial concentration: 0.0
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421966
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.00555555555555556
initial amount: NaN
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419826
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

423925
type: Reaction
kinetic law: 446973
product: 446961
reactant: 446949
fast: false
reversible: true

446973
type: KineticLaw
local parameters: 449354
local parameters: 449351
notes: kf*PKM_slash_PKM_synthesis-kb*PKM_slash_PKM_activator

449354
type: LocalParameter
units: 443196
value: 0.0

443220
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND

443208
type: SBMLUnit
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE

449351
type: LocalParameter
units: 443196
value: 1.5E-18

446961
type: SpeciesReference
stoichiometry: 1.0
species: 422046

422046
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0944444444444444
initial amount: NaN
in compartment: 418386

446949
type: SpeciesReference
stoichiometry: 1.0
species: 421966

426425
type: Reaction
kinetic law: 453472
product: 453460
product: 453448
reactant: 453436
fast: false
reversible: false

453472
type: KineticLaw
local parameters: 449588
notes: k3*PKM_slash_Ca_dot_detector_complex_slash_kenz_slash_kenz_cplx

449588
type: LocalParameter
units: 443196
value: 3.0E-16

453460
type: SpeciesReference
stoichiometry: 1.0
species: 422006

422006
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

453448
type: SpeciesReference
stoichiometry: 1.0
species: 421966

453436
type: SpeciesReference
stoichiometry: 1.0
species: 422026

422026
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

422086
type: Species
notes: This isn\'t explicitly present in the M&L model, but is obviously needed. I assume its conc is fixed at 1uM for now, which is a bit high. PLA2 is stim 7x by PIP2 @ 0.5 uM (Leslie and Channon BBA 1045:261(1990) Leslie and Channon say PIP2 is present at 0.1 - 0.2mol% range in membs, which comes to 50 nM. Ref is Majerus et al Cell 37 pp 701-703 1984 Lets use a lower level of 30 nM, same ref....
constant: true
boundary condition: true
has only substance units: false
initial concentration: 2.5
initial amount: NaN
in compartment: 418386

423445
type: Reaction
kinetic law: 445913
product: 445901
reactant: 445889
reactant: 445877
notes: going on the experience with CaM, we put the fast (high affinity) sites first. We only know (Stemmer and Klee) that the affinity is < 70 nM. Assuming 10 nM at first, we get kf = 2.78e-8, kb = 1. Try 20 nM. kf = 7e-9, kb = 1
fast: false
reversible: true

445913
type: KineticLaw
local parameters: 449258
local parameters: 449255
notes: kf*PP2B_slash_CaNAB*Ca^2-kb*PP2B_slash_CaNAB_minus_Ca2

449258
type: LocalParameter
units: 443196
value: 1.5E-15

449255
type: LocalParameter
units: 443232
value: 1.501254E-11

443268
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND

443256
type: SBMLUnit
exponent: -2.0
scale: -6
multipler: 1.0
kind: MOLE

443244
type: SBMLUnit
exponent: 3.0
scale: 0
multipler: 1.0
kind: LITRE

445901
type: SpeciesReference
stoichiometry: 1.0
species: 421026

421026
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

445889
type: SpeciesReference
stoichiometry: 2.0
species: 421646

421646
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.08
initial amount: NaN
in compartment: 418386

445877
type: SpeciesReference
stoichiometry: 1.0
species: 421006

421006
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 418386

419846
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

425025
type: Reaction
kinetic law: 450047
product: 450035
reactant: 450023
reactant: 450011
notes: Rates from Okada et al JBC 270:35 pp 20737 1995 Km = 0.70 to 0.85 uM, Vmax = 4.4 to 5.0 pmol/min. Unfortunately the amount of enzyme is not known, the prep is only partially purified. Time course of phosph is max within 30 sec, falls back within 20 min. Ref: Sasaoka et al JBC 269:51 32621 1994. Use k3 = 0.1 based on this tau.
fast: false
reversible: true

450047
type: KineticLaw
local parameters: 449454
local parameters: 449453
notes: k1*EGFR_slash_SHC*EGFR_slash_L_dot_EGFR-k2*EGFR_slash_L_dot_EGFR_slash_phosph_Shc_slash_phosph_Shc_cplx

449454
type: LocalParameter
units: 443196
value: 1.2E-15

449453
type: LocalParameter
units: 443280
value: 1.799955E-15

450035
type: SpeciesReference
stoichiometry: 1.0
species: 420086

420086
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

450023
type: SpeciesReference
stoichiometry: 1.0
species: 420046

420046
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

450011
type: SpeciesReference
stoichiometry: 1.0
species: 420106

420106
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 418386

422765
type: Reaction
kinetic law: 444370
product: 444358
reactant: 444346
notes: From Berstein et al JBC 267:12 8081-8088 1992, kcat for GTPase activity of Gq is only 0.8/min
fast: false
reversible: true

444370
type: KineticLaw
local parameters: 449122
local parameters: 449119
notes: kf*G_star_GTP-kb*G_star_GDP

449122
type: LocalParameter
units: 443196
value: 0.0

449119
type: LocalParameter
units: 443196
value: 1.995E-17

444358
type: SpeciesReference
stoichiometry: 1.0
species: 419106

419106
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

444346
type: SpeciesReference
stoichiometry: 1.0
species: 419086

419086
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

421346
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

425145
type: Reaction
kinetic law: 450364
product: 450352
reactant: 450340
reactant: 450327
fast: false
reversible: true

450364
type: KineticLaw
local parameters: 449464
local parameters: 449463
notes: k1*CaMKII_slash_CaMKII_minus_CaM*CaMKII_slash_tot_CaM_CaMKII-k2*CaMKII_slash_tot_CaM_CaMKII_slash_CaM_act_286_slash_CaM_act_286_cplx

449464
type: LocalParameter
units: 443196
value: 3.0E-15

449463
type: LocalParameter
units: 443280
value: 3.30102E-17

450352
type: SpeciesReference
stoichiometry: 1.0
species: 420486

420486
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

450340
type: SpeciesReference
stoichiometry: 1.0
species: 422285

422285
type: Species
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

450327
type: SpeciesReference
stoichiometry: 1.0
species: 420366

420366
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

419726
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

420786
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

421546
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 2.0
initial amount: NaN
in compartment: 418386

425705
type: Reaction
kinetic law: 451724
modifier: 451712
product: 451700
reactant: 451688
fast: false
reversible: false

451724
type: KineticLaw
local parameters: 449515
local parameters: 449514
notes: kcat*AC_slash_AC1_minus_CaM*AC_slash_ATP/(Km+AC_slash_ATP)

449515
type: LocalParameter
units: 443160
value: 20.0

443184
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exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE

443172
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE

449514
type: LocalParameter
units: 443196
value: 2.7E-14

421306
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

451700
type: SpeciesReference
stoichiometry: 1.0
species: 421286

421286
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

451688
type: SpeciesReference
stoichiometry: 1.0
species: 422205

422205
type: Species
notes: ATP is present in all cells between 2 and 10 mM. See Lehninger.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 5000.0
initial amount: NaN
in compartment: 418386

420466
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

419566
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

418786
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

420666
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 20.0
initial amount: NaN
in compartment: 418386

422246
type: Species
constant: true
boundary condition: true
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 418386

419026
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

420506
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

422665
type: Reaction
kinetic law: 444139
product: 444127
reactant: 444115
reactant: 444103
notes: this binding does not produce active PLC. This step was needed to implement the described (Smrcka et al) increase in affinity for Ca by PLC once Gq was bound. The kinetics are the same as the binding step for Ca-PLC to Gq. June 1996: Changed the kf to 4.2e-5 to 4.2e-6 to preserve balance around the reactions.
fast: false
reversible: true

444139
type: KineticLaw
local parameters: 449102
local parameters: 449099
notes: kf*PLCbeta_slash_PLC*G_star_GTP-kb*PLCbeta_slash_PLC_minus_Gq

449102
type: LocalParameter
units: 443196
value: 1.5E-15

449099
type: LocalParameter
units: 443280
value: 3.78E-15

444127
type: SpeciesReference
stoichiometry: 1.0
species: 419046

419046
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

444115
type: SpeciesReference
stoichiometry: 1.0
species: 419086

444103
type: SpeciesReference
stoichiometry: 1.0
species: 418946

418946
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.8
initial amount: NaN
in compartment: 418386

420166
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

425485
type: Reaction
kinetic law: 451186
product: 451174
product: 451162
reactant: 451150
fast: false
reversible: false

451186
type: KineticLaw
local parameters: 449495
notes: k3*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_neurogranin_slash_dephosph_neurogranin_cplx

449495
type: LocalParameter
units: 443196
value: 1.005E-15

451174
type: SpeciesReference
stoichiometry: 1.0
species: 422305

422305
type: Species
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

451162
type: SpeciesReference
stoichiometry: 1.0
species: 420726

420726
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 10.0
initial amount: NaN
in compartment: 418386

451150
type: SpeciesReference
stoichiometry: 1.0
species: 420786

423385
type: Reaction
kinetic law: 445769
product: 445757
reactant: 445744
reactant: 445732
notes: K inhib = 1nM from Cohen Ann Rev Bioch 1989, 4 nM from Foukes et al Assume 2 nM. kf /kb = 8.333e-4
fast: false
reversible: true

445769
type: KineticLaw
local parameters: 449246
local parameters: 449243
notes: kf*PP1_slash_I1_star_*PP1_minus_active-kb*PP1_slash_PP1_minus_I1_star_

449246
type: LocalParameter
units: 443196
value: 1.5E-16

449243
type: LocalParameter
units: 443280
value: 7.499655E-13

445757
type: SpeciesReference
stoichiometry: 1.0
species: 420866

420866
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

445744
type: SpeciesReference
stoichiometry: 1.0
species: 420546

420546
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.8
initial amount: NaN
in compartment: 418386

445732
type: SpeciesReference
stoichiometry: 1.0
species: 420846

420846
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.001
initial amount: NaN
in compartment: 418386

421186
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

424005
type: Reaction
kinetic law: 447169
product: 447157
product: 447145
reactant: 447132
fast: false
reversible: false

447169
type: KineticLaw
local parameters: 449362
notes: k3*PLA2_slash_PIP2_minus_PLA2_star__slash_kenz_slash_kenz_cplx

449362
type: LocalParameter
units: 443196
value: 1.656E-14

447157
type: SpeciesReference
stoichiometry: 1.0
species: 418666

418666
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

447145
type: SpeciesReference
stoichiometry: 1.0
species: 418586

418586
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

447132
type: SpeciesReference
stoichiometry: 1.0
species: 418686

418686
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

424765
type: Reaction
kinetic law: 449030
product: 449018
product: 449006
reactant: 448994
fast: false
reversible: false

449030
type: KineticLaw
local parameters: 449431
notes: k3*Ras_slash_GAP_slash_GAP_minus_inact_minus_ras_slash_GAP_minus_inact_minus_ras_cplx

449431
type: LocalParameter
units: 443196
value: 1.5E-14

449018
type: SpeciesReference
stoichiometry: 1.0
species: 419786

419786
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.01
initial amount: NaN
in compartment: 418386

449006
type: SpeciesReference
stoichiometry: 1.0
species: 419746

419746
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 418386

448994
type: SpeciesReference
stoichiometry: 1.0
species: 419806

419806
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

420186
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 418386

426105
type: Reaction
kinetic law: 452689
product: 452677
product: 452665
reactant: 452653
fast: false
reversible: false

452689
type: KineticLaw
local parameters: 449558
notes: k3*MKP3_slash_MKP3_synthesis_slash_kenz_slash_kenz_cplx

449558
type: LocalParameter
units: 443196
value: 1.5E-17

452677
type: SpeciesReference
stoichiometry: 1.0
species: 421786

421786
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0014
initial amount: NaN
in compartment: 418386

452665
type: SpeciesReference
stoichiometry: 1.0
species: 421726

421726
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.02
initial amount: NaN
in compartment: 418386

452653
type: SpeciesReference
stoichiometry: 1.0
species: 421806

421806
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

422985
type: Reaction
kinetic law: 444890
product: 444878
reactant: 444866
reactant: 444854
notes: We have no numbers for this. It is probably between the two extremes represented by the CaMKII phosph states, and I have used guesses based on this. kf=1e-4 kb=1 The reaction is based on Farnsworth et al Nature 376 524-527 1995 2 Aug 2004 Raised Kf from 60 to 200 to achieve higher MAPK activation following Ca stimulus for PKM models. 3 Aug 2004. Lowered Kf to 100.
fast: false
reversible: true

444890
type: KineticLaw
local parameters: 449166
local parameters: 449163
notes: kf*Ras_slash_inact_minus_GEF*CaM_minus_Ca4-kb*Ras_slash_CaM_minus_GEF

449166
type: LocalParameter
units: 443196
value: 1.5E-15

449163
type: LocalParameter
units: 443280
value: 2.99997E-13

444878
type: SpeciesReference
stoichiometry: 1.0
species: 419846

444866
type: SpeciesReference
stoichiometry: 1.0
species: 419966

419966
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

444854
type: SpeciesReference
stoichiometry: 1.0
species: 419666

419486
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

424485
type: Reaction
kinetic law: 448352
product: 448340
product: 448328
reactant: 448316
fast: false
reversible: false

448352
type: KineticLaw
local parameters: 449404
notes: k3*MAPK_slash_Raf_star__minus_GTP_minus_Ras_slash_Raf_star__minus_GTP_minus_Ras_dot_2_slash_Raf_star__minus_GTP_minus_Ras_dot_2_cplx

449404
type: LocalParameter
units: 443196
value: 4.5E-16

448340
type: SpeciesReference
stoichiometry: 1.0
species: 419446

419446
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

448328
type: SpeciesReference
stoichiometry: 1.0
species: 419366

419366
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

448316
type: SpeciesReference
stoichiometry: 1.0
species: 419486

421206
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

425365
type: Reaction
kinetic law: 450897
product: 450885
product: 450873
reactant: 450861
fast: false
reversible: false

450897
type: KineticLaw
local parameters: 449483
notes: k3*PP1_minus_active_slash_Deph_minus_thr306_slash_Deph_minus_thr306_cplx

449483
type: LocalParameter
units: 443196
value: 5.25E-16

450885
type: SpeciesReference
stoichiometry: 1.0
species: 420546

450873
type: SpeciesReference
stoichiometry: 1.0
species: 420346

420346
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 70.0
initial amount: NaN
in compartment: 418386

450861
type: SpeciesReference
stoichiometry: 1.0
species: 420606

420606
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

422465
type: Reaction
kinetic law: 443655
product: 443643
reactant: 443631
reactant: 443619
fast: false
reversible: true

443655
type: KineticLaw
local parameters: 449058
local parameters: 449055
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_cytosolic-kb*PLA2_slash_PIP2_minus_PLA2_star_

449058
type: LocalParameter
units: 443196
value: 7.5E-16

449055
type: LocalParameter
units: 443280
value: 1.799955E-18

443643
type: SpeciesReference
stoichiometry: 1.0
species: 418666

443631
type: SpeciesReference
stoichiometry: 1.0
species: 418606

418606
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.4
initial amount: NaN
in compartment: 418386

443619
type: SpeciesReference
stoichiometry: 1.0
species: 422086

423126
type: Reaction
kinetic law: 445178
product: 445166
reactant: 445154
notes: The only clue I have to these rates is from the time courses of the EGF activation, which is around 1 to 5 min. The dephosph would be expected to be of the same order, perhaps a bit longer. Lets use 0.002 which is about 8 min. Sep 17: The transient activation curve matches better with kf = 0.001
fast: false
reversible: true

445178
type: KineticLaw
local parameters: 449194
local parameters: 449191
notes: kf*Sos_slash_Sos_star_-kb*Sos_slash_Sos

449194
type: LocalParameter
units: 443196
value: 0.0

449191
type: LocalParameter
units: 443196
value: 1.5E-18

445166
type: SpeciesReference
stoichiometry: 1.0
species: 420246

420246
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.1
initial amount: NaN
in compartment: 418386

445154
type: SpeciesReference
stoichiometry: 1.0
species: 420226

420226
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

425925
type: Reaction
kinetic law: 452255
product: 452243
reactant: 452231
reactant: 452219
notes: Max activity ~10umol/min/mg in presence of lots of CaM. Affinity is low, 40 uM. k3 = 10, k2 = 40, k1 = (50/40) / 6e5.
fast: false
reversible: true

452255
type: KineticLaw
local parameters: 449542
local parameters: 449541
notes: k1*cAMP*AC_slash_CaM_dot_PDE1-k2*AC_slash_CaM_dot_PDE1_slash_CaM_dot_PDE1_slash_CaM_dot_PDE1_cplx

449542
type: LocalParameter
units: 443196
value: 6.0E-14

449541
type: LocalParameter
units: 443280
value: 1.89E-15

452243
type: SpeciesReference
stoichiometry: 1.0
species: 421606

421606
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

452231
type: SpeciesReference
stoichiometry: 1.0
species: 421586

421586
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

452219
type: SpeciesReference
stoichiometry: 1.0
species: 421286

425865
type: Reaction
kinetic law: 452110
product: 452098
product: 452086
reactant: 452074
fast: false
reversible: false

452110
type: KineticLaw
local parameters: 449537
notes: k3*AC_slash_cAMP_minus_PDE_star__slash_PDE_star__slash_PDE_star__cplx

449537
type: LocalParameter
units: 443196
value: 3.0E-14

452098
type: SpeciesReference
stoichiometry: 1.0
species: 421506

421506
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

452086
type: SpeciesReference
stoichiometry: 1.0
species: 421426

421426
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 325493.333333333
initial amount: NaN
in compartment: 418406

418406
type: Compartment
constant: true
size: 2.5E-21
spatial dimensions: 3.0

452074
type: SpeciesReference
stoichiometry: 1.0
species: 421526

421526
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

420566
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

425285
type: Reaction
kinetic law: 450702
product: 450690
product: 450678
reactant: 450666
fast: false
reversible: false

450702
type: KineticLaw
local parameters: 449477
notes: k3*PP1_minus_active_slash_Deph_minus_thr286_slash_Deph_minus_thr286_cplx

449477
type: LocalParameter
units: 443196
value: 5.25E-16

450690
type: SpeciesReference
stoichiometry: 1.0
species: 420546

450678
type: SpeciesReference
stoichiometry: 1.0
species: 420366

450666
type: SpeciesReference
stoichiometry: 1.0
species: 420566

426205
type: Reaction
kinetic law: 452931
product: 452919
reactant: 452907
reactant: 452895
notes: Rate consts from PKC-act-raf. This reaction activates GEF. It can lead to at least 2X stim of ras, and a 2X stim of MAPK over and above that obtained via direct phosph of c-raf. Note that it is a push-pull reaction, and there is also a contribution through the phosphorylation and inactivation of GAPs. The original PKC-act-raf rate consts are too fast. We lower K1 by 10 X
fast: false
reversible: true

452931
type: KineticLaw
local parameters: 449569
local parameters: 449566
notes: k1*Ras_slash_inact_minus_GEF*PKC_minus_active-k2*PKC_minus_active_slash_PKC_minus_act_minus_GEF_slash_PKC_minus_act_minus_GEF_cplx

449569
type: LocalParameter
units: 443196
value: 2.4E-14

449566
type: LocalParameter
units: 443280
value: 9.000045E-15

452919
type: SpeciesReference
stoichiometry: 1.0
species: 421866

421866
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

452907
type: SpeciesReference
stoichiometry: 1.0
species: 422325

422325
type: Species
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0934
initial amount: NaN
in compartment: 418386

452895
type: SpeciesReference
stoichiometry: 1.0
species: 419666

421486
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

423865
type: Reaction
kinetic law: 446853
product: 446841
reactant: 446829
fast: false
reversible: true

446853
type: KineticLaw
local parameters: 449342
local parameters: 449339
notes: kf*MKP3_slash_MKP_minus_3-kb*MKP3_slash_ubiquitination

449342
type: LocalParameter
units: 443196
value: 0.0

449339
type: LocalParameter
units: 443196
value: 7.5E-19

446841
type: SpeciesReference
stoichiometry: 1.0
species: 422226

422226
type: Species
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

446829
type: SpeciesReference
stoichiometry: 1.0
species: 421726

424585
type: Reaction
kinetic law: 448593
product: 448581
reactant: 448568
reactant: 448556
fast: false
reversible: true

449415
type: LocalParameter
units: 443196
value: 3.6E-14

449414
type: LocalParameter
units: 443280
value: 2.87415E-15

448581
type: SpeciesReference
stoichiometry: 1.0
species: 419566

448568
type: SpeciesReference
stoichiometry: 1.0
species: 419506

419506
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 418386

448556
type: SpeciesReference
stoichiometry: 1.0
species: 419426

419426
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

426325
type: Reaction
kinetic law: 453231
product: 453219
reactant: 453207
reactant: 453195
notes: Phorbol esters have little effect on AC1 or on the Gs-stimulation of AC2. So in this model we are only dealing with the increase in basal activation of AC2 induced by PKC k1 = 1.66e-6 k2 = 16 k3 =4
fast: false
reversible: true

453231
type: KineticLaw
local parameters: 449578
local parameters: 449577
notes: k1*AC_slash_AC2*PKC_minus_active-k2*PKC_minus_active_slash_phosph_minus_AC2_slash_phosph_minus_AC2_cplx

449578
type: LocalParameter
units: 443196
value: 2.4E-14

449577
type: LocalParameter
units: 443280
value: 9.000045E-16

453219
type: SpeciesReference
stoichiometry: 1.0
species: 421926

421926
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

453207
type: SpeciesReference
stoichiometry: 1.0
species: 422325

453195
type: SpeciesReference
stoichiometry: 1.0
species: 421386

421386
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.015
initial amount: NaN
in compartment: 418386

424845
type: Reaction
kinetic law: 449611
product: 449599
product: 449550
reactant: 449490
fast: false
reversible: false

449611
type: KineticLaw
local parameters: 449437
notes: k3*PKA_minus_active_slash_PKA_minus_phosph_minus_GEF_slash_PKA_minus_phosph_minus_GEF_cplx

449437
type: LocalParameter
units: 443196
value: 1.35E-14

449599
type: SpeciesReference
stoichiometry: 1.0
species: 419886

419886
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

449550
type: SpeciesReference
stoichiometry: 1.0
species: 419826

449490
type: SpeciesReference
stoichiometry: 1.0
species: 419906

419906
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

418486
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 8.46311111111111E-23
initial amount: NaN
in compartment: 418386

420686
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

420886
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

424405
type: Reaction
kinetic law: 448160
product: 448148
product: 448136
reactant: 448124
fast: false
reversible: false

448160
type: KineticLaw
local parameters: 449398
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx

449398
type: LocalParameter
units: 443196
value: 4.5E-16

448148
type: SpeciesReference
stoichiometry: 1.0
species: 419366

448136
type: SpeciesReference
stoichiometry: 1.0
species: 418846

448124
type: SpeciesReference
stoichiometry: 1.0
species: 419406

419406
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

422386
type: Reaction
kinetic law: 443389
product: 443377
reactant: 443365
reactant: 443353
notes: Need est of rate of assoc of Ca and PKC. Assume it is fast The original parameter-searched kf of 439.4 has been scaled by 1/6e8 to account for change of units to n. Kf now 8.16e-7, kb=.6085 Raised kf to 1e-6 to match Ca curve, kb to .5
fast: false
reversible: true

443389
type: KineticLaw
local parameters: 449034
local parameters: 449031
notes: kf*PKC_slash_PKC_minus_cytosolic*Ca-kb*PKC_slash_PKC_minus_Ca

449034
type: LocalParameter
units: 443196
value: 7.5E-16

449031
type: LocalParameter
units: 443280
value: 9.000045E-16

443377
type: SpeciesReference
stoichiometry: 1.0
species: 418426

418426
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.72077777777778E-17
initial amount: NaN
in compartment: 418386

443365
type: SpeciesReference
stoichiometry: 1.0
species: 421646

443353
type: SpeciesReference
stoichiometry: 1.0
species: 418526

418526
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 418386

423325
type: Reaction
kinetic law: 445636
product: 445624
reactant: 445612
reactant: 445600
notes: Use K3 = 21.5 uM here from Stemmer and Klee table 3. kb/kf =21.5 * 6e5 so kf = 7.75e-7, kb = 10
fast: false
reversible: true

445636
type: KineticLaw
local parameters: 449234
local parameters: 449231
notes: kf*CaM_minus_Ca3*Ca-kb*CaM_minus_Ca4

449234
type: LocalParameter
units: 443196
value: 1.5E-14

449231
type: LocalParameter
units: 443280
value: 6.975045E-16

445624
type: SpeciesReference
stoichiometry: 1.0
species: 419966

445612
type: SpeciesReference
stoichiometry: 1.0
species: 421646

445600
type: SpeciesReference
stoichiometry: 1.0
species: 420746

420746
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

422405
type: Reaction
kinetic law: 443437
product: 443425
reactant: 443413
reactant: 443401
notes: Need est of rate. Assume it is fast Obtained from param search kf raised 10 X : see Shinomura et al PNAS 88 5149-5153 1991. kf changed from 3.865e-7 to 2.0e-7 in line with closer analysis of Shinomura data. 26 June 1996: Corrected DAG data: reduce kf 15x from 2e-7 to 1.333e-8
fast: false
reversible: true

443437
type: KineticLaw
local parameters: 449038
local parameters: 449035
notes: kf*DAG*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_DAG

449038
type: LocalParameter
units: 443196
value: 1.29522E-14

449035
type: LocalParameter
units: 443280
value: 1.1999745E-17

443425
type: SpeciesReference
stoichiometry: 1.0
species: 418486

443413
type: SpeciesReference
stoichiometry: 1.0
species: 418426

443401
type: SpeciesReference
stoichiometry: 1.0
species: 418566

418566
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

423085
type: Reaction
kinetic law: 445094
product: 445082
reactant: 445070
reactant: 445058
notes: Sasaoka et al JBC 269:51 pp 32621 1994, table on pg 32623 indicates that this pathway accounts for about 50% of the GEF activation. (88% - 39%). Error is large, about 20%. Fig 1 is most useful in constraining rates. Chook et al JBC 271:48 pp 30472, 1996 say that the Kd is 0.2 uM for Shc binding to EGFR. The Kd for Grb direct binding is 0.7, so we\'ll ignore it.
fast: false
reversible: true

445094
type: KineticLaw
local parameters: 449186
local parameters: 449183
notes: kf*Sos_slash_Sos_dot_Grb2*EGFR_slash_SHC_star_-kb*Shc_star__dot_Sos_dot_Grb2

449186
type: LocalParameter
units: 443196
value: 1.5E-16

449183
type: LocalParameter
units: 443280
value: 7.499655E-16

445082
type: SpeciesReference
stoichiometry: 1.0
species: 419986

419986
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

445070
type: SpeciesReference
stoichiometry: 1.0
species: 420126

420126
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

445058
type: SpeciesReference
stoichiometry: 1.0
species: 420206

420206
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

422685
type: Reaction
kinetic law: 444187
product: 444175
reactant: 444163
reactant: 444151
notes: this step has a high affinity for Ca, from Smrcka et al. 0.1uM so kf /kb = 1/6e4 = 1.666e-5:1. See the Act-PLC-by-Gq reac. 11 Jun 1996: Raised kf to 5e-5 based on match to conc-eff curves from Smrcka et al.
fast: false
reversible: true

444187
type: KineticLaw
local parameters: 449106
local parameters: 449103
notes: kf*Ca*PLCbeta_slash_PLC_minus_Gq-kb*PLCbeta_slash_PLC_minus_Ca_minus_Gq

449106
type: LocalParameter
units: 443196
value: 1.5E-15

449103
type: LocalParameter
units: 443280
value: 4.499955E-14

444175
type: SpeciesReference
stoichiometry: 1.0
species: 419006

419006
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

444163
type: SpeciesReference
stoichiometry: 1.0
species: 419046

444151
type: SpeciesReference
stoichiometry: 1.0
species: 421646

422126
type: Species
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

424425
type: Reaction
kinetic law: 448208
product: 448196
reactant: 448184
reactant: 448172
notes: Kinetics are the same as for the craf-1* activity, ie., k1=1.1e-6, k2=.42, k3 =0.105 These are based on Force et al PNAS USA 91 1270-1274 1994. These parms cannot reach the observed 4X stim of MAPK. So lets increase the affinity, ie, raise k1 10X to 1.1e-5 Lets take it back down to where it was. Back up to 5X: 5.5e-6
fast: false
reversible: true

448208
type: KineticLaw
local parameters: 449400
local parameters: 449399
notes: k1*MAPK_slash_MAPKK*MAPK_slash_Raf_star__minus_GTP_minus_Ras-k2*MAPK_slash_Raf_star__minus_GTP_minus_Ras_slash_Raf_star__minus_GTP_minus_Ras_dot_1_slash_Raf_star__minus_GTP_minus_Ras_dot_1_cplx

449400
type: LocalParameter
units: 443196
value: 1.8E-15

449399
type: LocalParameter
units: 443280
value: 1.41426E-14

448196
type: SpeciesReference
stoichiometry: 1.0
species: 419466

419466
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

448184
type: SpeciesReference
stoichiometry: 1.0
species: 419446

448172
type: SpeciesReference
stoichiometry: 1.0
species: 419286

419286
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 418386

423065
type: Reaction
kinetic law: 445046
product: 445034
reactant: 445022
notes: See Helin and Beguinot JBC 266:13 1991 pg 8363-8368. In Fig 3 they have internalization tau about 10 min, equil at about 20% EGF available. So kf = 4x kb, and 1/(kf + kb) = 600 sec so kb = 1/3K = 3.3e-4, and kf = 1.33e-3. This doesn\'t take into account the unbound receptor, so we need to push the kf up a bit, to 0.002
fast: false
reversible: true

445046
type: KineticLaw
local parameters: 449182
local parameters: 449179
notes: kf*EGFR_slash_L_dot_EGFR-kb*EGFR_slash_Internal_L_dot_EGFR

449182
type: LocalParameter
units: 443196
value: 4.95E-19

449179
type: LocalParameter
units: 443196
value: 3.0E-18

445034
type: SpeciesReference
stoichiometry: 1.0
species: 420146

420146
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

445022
type: SpeciesReference
stoichiometry: 1.0
species: 420046

426165
type: Reaction
kinetic law: 452834
product: 452822
reactant: 452810
reactant: 452798
notes: Rate consts copied from PCK-act-raf This reaction inactivates GAP. The idea is from the Boguski and McCormick review.
fast: false
reversible: true

452834
type: KineticLaw
local parameters: 449563
local parameters: 449562
notes: k1*Ras_slash_GAP*PKC_minus_active-k2*PKC_minus_active_slash_PKC_minus_inact_minus_GAP_slash_PKC_minus_inact_minus_GAP_cplx

449563
type: LocalParameter
units: 443196
value: 2.4E-14

449562
type: LocalParameter
units: 443280
value: 9.000045E-15

452822
type: SpeciesReference
stoichiometry: 1.0
species: 421846

421846
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

452810
type: SpeciesReference
stoichiometry: 1.0
species: 422325

452798
type: SpeciesReference
stoichiometry: 1.0
species: 419786

420946
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

426125
type: Reaction
kinetic law: 452737
product: 452725
reactant: 452713
reactant: 452701
notes: Rate consts from Chen et al Biochem 32, 1032 (1993) k3 = k2 = 4 k1 = 9e-5 recalculated gives 1.666e-5, which is not very different. Looks like k3 is rate-limiting in this case: there is a huge amount of craf locked up in the enz complex. Let us assume a 10x higher Km, ie, lower affinity. k1 drops by 10x. Also changed k2 to 4x k3. Lowerd k1 to 1e-6 to balance 10X DAG sensitivity of PKC 3 Aug 2004. Lowered Km from 66.66 to 3.33, to match that of PKC-inact-GAP
fast: false
reversible: true

452737
type: KineticLaw
local parameters: 449560
local parameters: 449559
notes: k1*MAPK_slash_craf_minus_1*PKC_minus_active-k2*PKC_minus_active_slash_PKC_minus_act_minus_raf_slash_PKC_minus_act_minus_raf_cplx

449560
type: LocalParameter
units: 443196
value: 2.4E-14

449559
type: LocalParameter
units: 443280
value: 1.499985E-15

452725
type: SpeciesReference
stoichiometry: 1.0
species: 421826

421826
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

452713
type: SpeciesReference
stoichiometry: 1.0
species: 422325

452701
type: SpeciesReference
stoichiometry: 1.0
species: 419246

419246
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 418386

423185
type: Reaction
kinetic law: 445323
product: 445311
reactant: 445299
reactant: 445287
notes: Again, we refer to Homma et al and Wahl et al, for preference using Wahl. Half-Max of the phosph form is at 316 nM. Use kb of 10 as this is likely to be pretty fast. Did some curve comparisons, and instead of 316 nM giving a kf of 5.27e-5, we will use 8e-5 for kf. 16 Sep 97. As we are now phosphorylating the Ca-bound form, equils have shifted. kf should now be 2e-5 to match the curves.
fast: false
reversible: true

445323
type: KineticLaw
local parameters: 449206
local parameters: 449203
notes: kf*Ca*PLC_g_slash_PLC_G_star_-kb*PLC_g_slash_Ca_dot_PLC_g_star_

449206
type: LocalParameter
units: 443196
value: 1.5E-14

449203
type: LocalParameter
units: 443280
value: 1.799955E-14

445311
type: SpeciesReference
stoichiometry: 1.0
species: 420326

420326
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

445299
type: SpeciesReference
stoichiometry: 1.0
species: 420286

420286
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

445287
type: SpeciesReference
stoichiometry: 1.0
species: 421646

422566
type: Reaction
kinetic law: 443922
product: 443910
reactant: 443898
reactant: 443886
notes: Affinity for Ca = 1uM without AlF, 0.1 with: from Smrcka et al science 251 pp 804-807 1991 so [Ca].kf = kb so kb/kf = 1 * 6e5 = 1/1.66e-6 11 June 1996: Raised affinity to 5e-6 to maintain balance. See notes.
fast: false
reversible: true

443922
type: KineticLaw
local parameters: 449082
local parameters: 449079
notes: kf*Ca*PLCbeta_slash_PLC-kb*PLCbeta_slash_PLC_minus_Ca

449082
type: LocalParameter
units: 443196
value: 1.5E-15

449079
type: LocalParameter
units: 443280
value: 4.499955E-15

443910
type: SpeciesReference
stoichiometry: 1.0
species: 418966

418966
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

443898
type: SpeciesReference
stoichiometry: 1.0
species: 418946

443886
type: SpeciesReference
stoichiometry: 1.0
species: 421646

425905
type: Reaction
kinetic law: 452207
product: 452195
product: 452183
reactant: 452170
fast: false
reversible: false

452207
type: KineticLaw
local parameters: 449540
notes: k3*AC_slash_PDE1_slash_PDE1_slash_PDE1_cplx

449540
type: LocalParameter
units: 443196
value: 2.5005E-15

452195
type: SpeciesReference
stoichiometry: 1.0
species: 421546

452183
type: SpeciesReference
stoichiometry: 1.0
species: 421426

452170
type: SpeciesReference
stoichiometry: 1.0
species: 421566

421566
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

425565
type: Reaction
kinetic law: 451378
product: 451366
product: 451354
reactant: 451342
fast: false
reversible: false

451378
type: KineticLaw
local parameters: 449501
notes: k3*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_minus_PP1_minus_I_star__slash_dephosph_minus_PP1_minus_I_star__cplx

449501
type: LocalParameter
units: 443196
value: 5.1E-16

451366
type: SpeciesReference
stoichiometry: 1.0
species: 422305

451354
type: SpeciesReference
stoichiometry: 1.0
species: 420886

451342
type: SpeciesReference
stoichiometry: 1.0
species: 419606

419606
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

422725
type: Reaction
kinetic law: 444284
product: 444271
product: 444259
reactant: 444247
notes: kf = kg1 = 0.01/sec, kb = 0. This is the basal exchange of GTP for GDP.
fast: false
reversible: true

444284
type: KineticLaw
local parameters: 449114
local parameters: 449111
notes: kf*Gq_slash_G_minus_GDP-kb*G_star_GTP*BetaGamma

449114
type: LocalParameter
units: 443280
value: 0.0

449111
type: LocalParameter
units: 443196
value: 1.5E-19

444271
type: SpeciesReference
stoichiometry: 1.0
species: 419066

419066
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

444259
type: SpeciesReference
stoichiometry: 1.0
species: 419086

444247
type: SpeciesReference
stoichiometry: 1.0
species: 419126

419126
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 418386

423685
type: Reaction
kinetic law: 446479
product: 446467
reactant: 446455
notes: Random rate.
fast: false
reversible: true

446479
type: KineticLaw
local parameters: 449306
local parameters: 449303
notes: kf*AC_slash_AC2_star_-kb*AC_slash_AC2

449306
type: LocalParameter
units: 443196
value: 0.0

449303
type: LocalParameter
units: 443196
value: 1.5E-16

446467
type: SpeciesReference
stoichiometry: 1.0
species: 421386

446455
type: SpeciesReference
stoichiometry: 1.0
species: 421346

425765
type: Reaction
kinetic law: 451869
modifier: 451857
product: 451845
reactant: 451832
fast: false
reversible: false

451869
type: KineticLaw
local parameters: 449525
local parameters: 449522
notes: kcat*AC_slash_AC1_minus_Gs*AC_slash_ATP/(Km+AC_slash_ATP)

449525
type: LocalParameter
units: 443160
value: 20.0

449522
type: LocalParameter
units: 443196
value: 2.7E-14

421406
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

451845
type: SpeciesReference
stoichiometry: 1.0
species: 421286

451832
type: SpeciesReference
stoichiometry: 1.0
species: 422205

418726
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

423545
type: Reaction
kinetic law: 446154
product: 446142
reactant: 446130
reactant: 446118
notes: For now let us set this to the same Km (1e-7M) as site B. This gives kf/kb = .7e-7M * 1e6 / (6e5^2) : 1/(6e5^2) = 2e-13:2.77e-12 Smith et al have better values. They say that this is cooperative, so the consts are now kf/kb =8.3e-4
fast: false
reversible: true

446154
type: KineticLaw
local parameters: 449278
local parameters: 449275
notes: kf*PKA_slash_R2C2_minus_cAMP*cAMP-kb*PKA_slash_R2C2_minus_cAMP2

449278
type: LocalParameter
units: 443196
value: 4.95E-14

449275
type: LocalParameter
units: 443280
value: 8.1E-14

446142
type: SpeciesReference
stoichiometry: 1.0
species: 421146

421146
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

446130
type: SpeciesReference
stoichiometry: 1.0
species: 421286

446118
type: SpeciesReference
stoichiometry: 1.0
species: 421126

421126
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

423145
type: Reaction
kinetic law: 445226
product: 445214
reactant: 445202
reactant: 445190
notes: As there are 2 SH3 domains, this reaction could be 2nd order. I have a Kd of 22 uM from peptide binding (Lemmon et al JBC 269:50 pg 31653). However, Chook et al JBC 271:48 pg30472 say it is 0.4uM with purified proteins, so we believe them. They say it is 1:1 binding.
fast: false
reversible: true

445226
type: KineticLaw
local parameters: 449198
local parameters: 449195
notes: kf*Sos_slash_Grb2*Sos_slash_Sos-kb*Sos_slash_Sos_dot_Grb2

449198
type: LocalParameter
units: 443196
value: 2.52E-17

449195
type: LocalParameter
units: 443280
value: 3.75003E-17

445214
type: SpeciesReference
stoichiometry: 1.0
species: 420206

445202
type: SpeciesReference
stoichiometry: 1.0
species: 420246

445190
type: SpeciesReference
stoichiometry: 1.0
species: 420186

423645
type: Reaction
kinetic law: 446395
product: 446383
reactant: 446371
reactant: 446359
notes: This has to be set to zero for matching the expts in vitro. In vivo we need to consider the inhibition though. kf = 1e-5 kb = 1
fast: false
reversible: true

446395
type: KineticLaw
local parameters: 449298
local parameters: 449295
notes: kf*PKA_minus_active*PKA_slash_PKA_minus_inhibitor-kb*PKA_slash_inhibited_minus_PKA

449298
type: LocalParameter
units: 443196
value: 1.5E-15

449295
type: LocalParameter
units: 443280
value: 9.000045E-14

446383
type: SpeciesReference
stoichiometry: 1.0
species: 421266

421266
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

446371
type: SpeciesReference
stoichiometry: 1.0
species: 421246

421246
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.25
initial amount: NaN
in compartment: 418386

446359
type: SpeciesReference
stoichiometry: 1.0
species: 419886

424365
type: Reaction
kinetic law: 448064
product: 448052
product: 448040
reactant: 448028
fast: false
reversible: false

448064
type: KineticLaw
local parameters: 449395
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx

449395
type: LocalParameter
units: 443196
value: 4.5E-16

448052
type: SpeciesReference
stoichiometry: 1.0
species: 419366

448040
type: SpeciesReference
stoichiometry: 1.0
species: 419346

419346
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

448028
type: SpeciesReference
stoichiometry: 1.0
species: 419386

419386
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

418746
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

425745
type: Reaction
kinetic law: 451820
modifier: 451808
product: 451796
reactant: 451784
fast: false
reversible: false

451820
type: KineticLaw
local parameters: 449521
local parameters: 449518
notes: kcat*AC_slash_AC2_minus_Gs*AC_slash_ATP/(Km+AC_slash_ATP)

449521
type: LocalParameter
units: 443160
value: 20.0

449518
type: LocalParameter
units: 443196
value: 2.7E-14

421366
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

451796
type: SpeciesReference
stoichiometry: 1.0
species: 421286

451784
type: SpeciesReference
stoichiometry: 1.0
species: 422205

424225
type: Reaction
kinetic law: 447702
product: 447689
reactant: 447677
reactant: 447665
notes: See Porfiri and McCormick JBC 271:10 pp5871 1996 for the existence of this step. We\'ll take the rates from the ones used for the phosph of Raf by MAPK. Sep 17 1997: The transient activation curve matches better with k1 up by 10 x.
fast: false
reversible: true

447702
type: KineticLaw
local parameters: 449382
local parameters: 449381
notes: k1*Sos_slash_Sos*MAPK_star_-k2*MAPK_star__slash_phosph_Sos_slash_phosph_Sos_cplx

449382
type: LocalParameter
units: 443196
value: 6.0E-14

449381
type: LocalParameter
units: 443280
value: 2.925045E-14

447689
type: SpeciesReference
stoichiometry: 1.0
species: 418906

418906
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

447677
type: SpeciesReference
stoichiometry: 1.0
species: 418846

447665
type: SpeciesReference
stoichiometry: 1.0
species: 420246

422605
type: Reaction
kinetic law: 443994
product: 443982
reactant: 443970
notes: These rates are the same as for degrading IP3, but I am sure that they could be improved. Lets double kf to 0.2, since the amount of DAG in the cell should be <= 1uM. Need to double it again, for the same reason. kf now 0.5 27 June 1996 kf is now 0.02 to get 50 sec time course 30 Aug 1997: Raised kf to 0.11 to accomodate PLC_gamma 27 Mar 1998: kf now 0.15 for PLC_gamma
fast: false
reversible: true

443994
type: KineticLaw
local parameters: 449090
local parameters: 449087
notes: kf*DAG-kb*PLCbeta_slash_PC

449090
type: LocalParameter
units: 443196
value: 0.0

449087
type: LocalParameter
units: 443196
value: 2.25E-16

443982
type: SpeciesReference
stoichiometry: 1.0
species: 422146

422146
type: Species
notes: Phosphatidylcholine is the main (around 55%) metabolic product of DAG, follwed by PE (around 25%). Ref is Welsh and Cabot, JCB35:231-245(1987)
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418406

443970
type: SpeciesReference
stoichiometry: 1.0
species: 418566

425105
type: Reaction
kinetic law: 450266
product: 450254
reactant: 450242
reactant: 450230
notes: Rates from autocamtide phosphorylation, from Hanson and Schulman JBC 267:24 17216-17224 1992. Jan 1 1998: Speed up 12x to match fig 5.
fast: false
reversible: true

450266
type: KineticLaw
local parameters: 449461
local parameters: 449460
notes: k1*CaMKII_slash_CaMKII_minus_thr286*CaMKII_slash_tot_CaM_CaMKII-k2*CaMKII_slash_tot_CaM_CaMKII_slash_CaM_act_305_slash_CaM_act_305_cplx

449461
type: LocalParameter
units: 443196
value: 3.6E-14

449460
type: LocalParameter
units: 443280
value: 3.961305E-16

450254
type: SpeciesReference
stoichiometry: 1.0
species: 420466

450242
type: SpeciesReference
stoichiometry: 1.0
species: 422285

450230
type: SpeciesReference
stoichiometry: 1.0
species: 420426

420426
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

424065
type: Reaction
kinetic law: 447316
product: 447304
reactant: 447291
reactant: 447279
notes: 10 X raise oct 22 12 X raise oct 24 + conversion to k2 =4 * k3
fast: false
reversible: true

447316
type: KineticLaw
local parameters: 449367
local parameters: 449366
notes: k1*PLA2_slash_APC*PLA2_slash_DAG_minus_Ca_minus_PLA2_star_-k2*PLA2_slash_DAG_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx

449367
type: LocalParameter
units: 443196
value: 3.6E-13

449366
type: LocalParameter
units: 443280
value: 2.250045E-14

447304
type: SpeciesReference
stoichiometry: 1.0
species: 418766

418766
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

447291
type: SpeciesReference
stoichiometry: 1.0
species: 418746

447279
type: SpeciesReference
stoichiometry: 1.0
species: 422066

422066
type: Species
notes: arachodonylphosphatidylcholine is the favoured substrate from Wijkander and Sundler, JBC 202 pp 873-880, 1991. Their assay used 30 uM substrate, which is what the kinetics in this model are based on. For the later model we should locate a more realistic value for APC.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 30.0
initial amount: NaN
in compartment: 418386

426345
type: Reaction
kinetic law: 453279
product: 453267
product: 453255
reactant: 453243
fast: false
reversible: false

453279
type: KineticLaw
local parameters: 449579
notes: k3*PKC_minus_active_slash_phosph_minus_AC2_slash_phosph_minus_AC2_cplx

449579
type: LocalParameter
units: 443196
value: 6.0E-15

453267
type: SpeciesReference
stoichiometry: 1.0
species: 422325

453255
type: SpeciesReference
stoichiometry: 1.0
species: 421346

453243
type: SpeciesReference
stoichiometry: 1.0
species: 421926

426045
type: Reaction
kinetic law: 452545
product: 452533
reactant: 452521
reactant: 452509
notes: The original kinetics have been modified to obey the k2 = 4 * k3 rule, while keeping kcat and Km fixed. As noted in the NOTES, the only constraining data point is the time course of MAPK dephosphorylation, which this model satisfies. It would be nice to have more accurate estimates of rate consts and MKP-1 levels from the literature. Effective Km : 67 nM kcat = 1.43 umol/min/mg Km for MKP3 is set to 267 nM, twice as high as MKP1 version, to lessen substrate saturation.
fast: false
reversible: true

452545
type: KineticLaw
local parameters: 449554
local parameters: 449553
notes: k1*MAPK_slash_MAPK_minus_tyr*MKP3_slash_MKP_minus_3-k2*MKP3_slash_MKP_minus_3_slash_MKP3_minus_tyr_minus_deph_slash_MKP3_minus_tyr_minus_deph_cplx

449554
type: LocalParameter
units: 443196
value: 2.4E-14

449553
type: LocalParameter
units: 443280
value: 2.99997E-15

452533
type: SpeciesReference
stoichiometry: 1.0
species: 421766

421766
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

452521
type: SpeciesReference
stoichiometry: 1.0
species: 421726

452509
type: SpeciesReference
stoichiometry: 1.0
species: 419346

422945
type: Reaction
kinetic law: 444806
product: 444794
reactant: 444782
notes: This is extremely slow (1e-4), but it is significant as so little GAP actually gets complexed with it that the total GTP turnover rises only by 2-3 X (see Gibbs et al, JBC 265(33) 20437-20422) and Eccleston et al JBC 268(36) 27012-27019 kf = 1e-4
fast: false
reversible: true

444806
type: KineticLaw
local parameters: 449158
local parameters: 449155
notes: kf*Ras_slash_GTP_minus_Ras-kb*Ras_slash_GDP_minus_Ras

449158
type: LocalParameter
units: 443196
value: 0.0

449155
type: LocalParameter
units: 443196
value: 1.5E-19

444794
type: SpeciesReference
stoichiometry: 1.0
species: 419746

444782
type: SpeciesReference
stoichiometry: 1.0
species: 419726

425445
type: Reaction
kinetic law: 451090
product: 451078
product: 451066
reactant: 451054
fast: false
reversible: false

451090
type: KineticLaw
local parameters: 449489
notes: k3*PP1_minus_active_slash_Deph_thr286b_slash_Deph_thr286b_cplx

449489
type: LocalParameter
units: 443196
value: 5.25E-16

451078
type: SpeciesReference
stoichiometry: 1.0
species: 420546

451066
type: SpeciesReference
stoichiometry: 1.0
species: 420346

451054
type: SpeciesReference
stoichiometry: 1.0
species: 420646

420646
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

423345
type: Reaction
kinetic law: 445684
product: 445672
reactant: 445660
reactant: 445648
notes: Surprisingly, no direct info on rates from neurogranin at this time. These rates are based on GAP-43 binding studies. As GAP-43 and neurogranin share near identity in the CaM/PKC binding regions, and also similarity in phosph and dephosph rates, I am borrowing GAP-43 kinetic info. See Alexander et al JBC 262:13 6108-6113 1987
fast: false
reversible: true

445684
type: KineticLaw
local parameters: 449238
local parameters: 449235
notes: kf*CaM_slash_neurogranin*CaM_slash_CaM-kb*CaM_slash_neurogranin_minus_CaM

449238
type: LocalParameter
units: 443196
value: 1.5E-15

449235
type: LocalParameter
units: 443280
value: 4.499955E-16

445672
type: SpeciesReference
stoichiometry: 1.0
species: 420686

445660
type: SpeciesReference
stoichiometry: 1.0
species: 420666

445648
type: SpeciesReference
stoichiometry: 1.0
species: 420726

418546
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0555555555555556
initial amount: NaN
in compartment: 418386

426005
type: Reaction
kinetic law: 452448
product: 452436
reactant: 452424
reactant: 452412
notes: See MKP1-tyr-deph Km is twice as high to avoid saturation.
fast: false
reversible: true

452448
type: KineticLaw
local parameters: 449551
local parameters: 449548
notes: k1*MAPK_star_*MKP3_slash_MKP_minus_3-k2*MKP3_slash_MKP_minus_3_slash_MKP3_minus_thr_minus_deph_slash_MKP3_minus_thr_minus_deph_cplx

449551
type: LocalParameter
units: 443196
value: 2.4E-14

449548
type: LocalParameter
units: 443280
value: 2.99997E-15

452436
type: SpeciesReference
stoichiometry: 1.0
species: 421746

421746
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

452424
type: SpeciesReference
stoichiometry: 1.0
species: 421726

452412
type: SpeciesReference
stoichiometry: 1.0
species: 418846

426265
type: Reaction
kinetic law: 453075
product: 453063
product: 453051
reactant: 453039
fast: false
reversible: false

453075
type: KineticLaw
local parameters: 449573
notes: k3*PKC_minus_active_slash_PKC_minus_phosph_minus_neurogranin_slash_PKC_minus_phosph_minus_neurogranin_cplx

449573
type: LocalParameter
units: 443196
value: 8.7E-16

453063
type: SpeciesReference
stoichiometry: 1.0
species: 422325

453051
type: SpeciesReference
stoichiometry: 1.0
species: 420706

420706
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

453039
type: SpeciesReference
stoichiometry: 1.0
species: 421886

421886
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

424685
type: Reaction
kinetic law: 448835
product: 448823
product: 448810
reactant: 448798
fast: false
reversible: false

448835
type: KineticLaw
local parameters: 449422
notes: k3*Ras_slash_GEF_minus_Gprot_minus_bg_slash_GEF_minus_bg_act_minus_ras_slash_GEF_minus_bg_act_minus_ras_cplx

449422
type: LocalParameter
units: 443196
value: 3.0E-17

448823
type: SpeciesReference
stoichiometry: 1.0
species: 419626

419626
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

448810
type: SpeciesReference
stoichiometry: 1.0
species: 419726

448798
type: SpeciesReference
stoichiometry: 1.0
species: 419646

419646
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

421086
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

421446
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

425405
type: Reaction
kinetic law: 450993
product: 450981
product: 450969
reactant: 450957
fast: false
reversible: false

450993
type: KineticLaw
local parameters: 449486
notes: k3*PP1_minus_active_slash_Deph_minus_thr286c_slash_Deph_minus_thr286c_cplx

449486
type: LocalParameter
units: 443196
value: 5.25E-16

450981
type: SpeciesReference
stoichiometry: 1.0
species: 420546

450969
type: SpeciesReference
stoichiometry: 1.0
species: 420446

420446
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

450957
type: SpeciesReference
stoichiometry: 1.0
species: 420626

420626
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

425085
type: Reaction
notes: Mainly Homma et al JBC 263:14 1988 pp 6592, but these parms are the Ca-stimulated form. It is not clear whether the enzyme is activated by tyrosine phosphorylation at this point or not. Wahl et al JBC 267:15 10447-10456 1992 say that this has 7X higher affinity for substrate than control.
fast: false
product: 450181
reactant: 450169
kinetic law: 450218
product: 450194
modifier: 450206
reversible: false

450181
type: SpeciesReference
stoichiometry: 1.0
species: 418566

450169
type: SpeciesReference
stoichiometry: 1.0
species: 422166

422166
type: Species
constant: true
boundary condition: true
has only substance units: false
initial concentration: 10.0
initial amount: NaN
in compartment: 418386

450218
type: KineticLaw
local parameters: 449459
local parameters: 449458
notes: kcat*PLC_g_slash_Ca_dot_PLC_g_star_*PIP2/(Km+PIP2)

449459
type: LocalParameter
units: 443160
value: 19.7916666666667

449458
type: LocalParameter
units: 443196
value: 8.55E-14

450194
type: SpeciesReference
stoichiometry: 1.0
species: 418926

418926
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.73
initial amount: NaN
in compartment: 418386

424245
type: Reaction
kinetic law: 447750
product: 447738
product: 447726
reactant: 447714
fast: false
reversible: false

447750
type: KineticLaw
local parameters: 449383
notes: k3*MAPK_star__slash_phosph_Sos_slash_phosph_Sos_cplx

449383
type: LocalParameter
units: 443196
value: 1.5E-14

447738
type: SpeciesReference
stoichiometry: 1.0
species: 418846

447726
type: SpeciesReference
stoichiometry: 1.0
species: 420226

447714
type: SpeciesReference
stoichiometry: 1.0
species: 418906

419326
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

423285
type: Reaction
kinetic law: 445540
product: 445528
reactant: 445516
reactant: 445504
notes: Lets use the fast rate consts here. Since the rates are so different, I am not sure whether the order is relevant. These correspond to the TR2C fragment. We use the Martin et al rates here, plus the Drabicowski binding consts. All are scaled by 3X to cell temp. kf = 2e-10 kb = 72 Stemmer & Klee: K1=.9, K2=1.1. Assume 1.0uM for both. kb/kf=3.6e11. If kb=72, kf = 2e-10 (Exactly the same !)....
fast: false
reversible: true

445540
type: KineticLaw
local parameters: 449226
local parameters: 449223
notes: kf*CaM_slash_CaM*Ca^2-kb*CaM_minus_TR2_minus_Ca2

449226
type: LocalParameter
units: 443196
value: 1.08E-13

449223
type: LocalParameter
units: 443232
value: 1.08000135E-13

445528
type: SpeciesReference
stoichiometry: 1.0
species: 420766

420766
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

445516
type: SpeciesReference
stoichiometry: 2.0
species: 421646

445504
type: SpeciesReference
stoichiometry: 1.0
species: 420666

425965
type: Reaction
kinetic law: 452352
product: 452340
reactant: 452328
reactant: 452316
fast: false
reversible: true

452352
type: KineticLaw
local parameters: 449545
local parameters: 449544
notes: k1*MKP3_slash_nucleotides*MKP3_slash_nuc_MAPK_star_-k2*MKP3_slash_nuc_MAPK_star__slash_act_transcription_slash_act_transcription_cplx

449545
type: LocalParameter
units: 443196
value: 2.4E-17

449544
type: LocalParameter
units: 443280
value: 7.50006E-18

452340
type: SpeciesReference
stoichiometry: 1.0
species: 421706

421706
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

452328
type: SpeciesReference
stoichiometry: 1.0
species: 421686

421686
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

452316
type: SpeciesReference
stoichiometry: 1.0
species: 422206

422206
type: Species
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.2
initial amount: NaN
in compartment: 418386

424445
type: Reaction
kinetic law: 448256
product: 448244
product: 448232
reactant: 448220
fast: false
reversible: false

448256
type: KineticLaw
local parameters: 449401
notes: k3*MAPK_slash_Raf_star__minus_GTP_minus_Ras_slash_Raf_star__minus_GTP_minus_Ras_dot_1_slash_Raf_star__minus_GTP_minus_Ras_dot_1_cplx

449401
type: LocalParameter
units: 443196
value: 4.5E-16

448244
type: SpeciesReference
stoichiometry: 1.0
species: 419446

448232
type: SpeciesReference
stoichiometry: 1.0
species: 419426

448220
type: SpeciesReference
stoichiometry: 1.0
species: 419466

422825
type: Reaction
product: 444500
reactant: 444487
product: 444513
fast: false
kinetic law: 444539
product: 444526
reversible: true
notes: This is the kcat==k3 stage of the Rec-Glu ezymatic activation of Gq. From Berstein et al actiation is at .35 - 0.7/min From Fay et al Biochem 30 5066-5075 1991 kf = .01/sec From Nakamura et al J physiol Lond 474:1 35-41 1994 see time courses. Also (Berstein) 15-40% of gprot is in GTP-bound form on stim.

444500
type: SpeciesReference
stoichiometry: 1.0
species: 419086

444487
type: SpeciesReference
stoichiometry: 1.0
species: 419206

419206
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

444513
type: SpeciesReference
stoichiometry: 1.0
species: 419066

444539
type: KineticLaw
local parameters: 449134
local parameters: 449131
notes: kf*Gq_slash_Rec_minus_Glu_minus_Gq-kb*G_star_GTP*BetaGamma*Gq_slash_Rec_minus_Glu

449134
type: LocalParameter
units: 443232
value: 0.0

449131
type: LocalParameter
units: 443196
value: 1.5E-17

444526
type: SpeciesReference
stoichiometry: 1.0
species: 419166

419166
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

422425
type: Reaction
kinetic law: 443510
product: 443498
reactant: 443486
notes: Raise kb from .087 to 0.1 to match data from Shinomura et al. Lower kf from 1.155 to 1.0 to match data from Shinomura et al.
fast: false
reversible: true

443510
type: KineticLaw
local parameters: 449046
local parameters: 449043
notes: kf*PKC_slash_PKC_minus_Ca_minus_DAG-kb*PKC_slash_PKC_minus_DAG_minus_memb_star_

449046
type: LocalParameter
units: 443196
value: 1.5E-16

449043
type: LocalParameter
units: 443196
value: 1.5E-15

443498
type: SpeciesReference
stoichiometry: 1.0
species: 418466

418466
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 9.43511111111111E-21
initial amount: NaN
in compartment: 418386

443486
type: SpeciesReference
stoichiometry: 1.0
species: 418486

421626
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

425325
type: Reaction
kinetic law: 450799
product: 450787
product: 450775
reactant: 450763
fast: false
reversible: false

450799
type: KineticLaw
local parameters: 449480
notes: k3*PP1_minus_active_slash_Deph_minus_thr305_slash_Deph_minus_thr305_cplx

449480
type: LocalParameter
units: 443196
value: 5.25E-16

450787
type: SpeciesReference
stoichiometry: 1.0
species: 420546

450775
type: SpeciesReference
stoichiometry: 1.0
species: 420426

450763
type: SpeciesReference
stoichiometry: 1.0
species: 420586

420586
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

422745
type: Reaction
kinetic law: 444333
product: 444320
reactant: 444308
reactant: 444296
notes: kf == kg3 = 1e-5 /cell/sec. As usual, there is no back-reaction kb = 0
fast: false
reversible: true

444333
type: KineticLaw
local parameters: 449118
local parameters: 449115
notes: kf*G_star_GDP*BetaGamma-kb*Gq_slash_G_minus_GDP

449118
type: LocalParameter
units: 443196
value: 0.0

449115
type: LocalParameter
units: 443280
value: 9.000045E-15

444320
type: SpeciesReference
stoichiometry: 1.0
species: 419126

444308
type: SpeciesReference
stoichiometry: 1.0
species: 419066

444296
type: SpeciesReference
stoichiometry: 1.0
species: 419106

424305
type: Reaction
kinetic law: 447907
product: 447895
reactant: 447883
reactant: 447871
notes: From Sternweis et al, Phil Trans R Soc Lond 1992, and the values from other refs eg Homma et al JBC 263(14) pp6592 1988 match. k1 = 5e-5/sec k2 = 240/sec; now 120/sec k3 = 60/sec; now 30/sec Note that the wording in Sternweis et al is ambiguous wr. to the Km for Gq vs non-Gq states of PLC. K1 is still a bit too low. Raise to 7e-5 9 Jun 1996: k1 was 0.0002, changed to 5e-5
fast: false
reversible: true

447907
type: KineticLaw
local parameters: 449388
local parameters: 449387
notes: k1*PIP2*PLCbeta_slash_PLC_minus_Ca_minus_Gq-k2*PLCbeta_slash_PLC_minus_Ca_minus_Gq_slash_PLCb_minus_Ca_minus_Gq_slash_PLCb_minus_Ca_minus_Gq_cplx

449388
type: LocalParameter
units: 443196
value: 2.88E-13

449387
type: LocalParameter
units: 443280
value: 7.199955E-14

447895
type: SpeciesReference
stoichiometry: 1.0
species: 419026

447883
type: SpeciesReference
stoichiometry: 1.0
species: 419006

447871
type: SpeciesReference
stoichiometry: 1.0
species: 422166

424605
type: Reaction
kinetic law: 448641
product: 448629
product: 448617
reactant: 448605
fast: false
reversible: false

449416
type: LocalParameter
units: 443196
value: 9.0E-15

448629
type: SpeciesReference
stoichiometry: 1.0
species: 419506

448617
type: SpeciesReference
stoichiometry: 1.0
species: 419286

448605
type: SpeciesReference
stoichiometry: 1.0
species: 419566

443340
type: SBMLUnit
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE

418372
type: Compartment
constant: true
size: 1.0E-18
spatial dimensions: 3.0

422805
type: Reaction
kinetic law: 444474
product: 444461
reactant: 444448
reactant: 444435
notes: From Fay et al kb3 = kb = 1.06e-3 which is rather slow. k+1 = kf = 2.8e7 /M/sec= 4.67e-5/sec use 5e-5. However, the Kd from Martin et al may be more appropriate, as this is Glu not the system from Fay. kf = 2.8e-5, kb = 10 Let us compromise. since we have the Fay model, keep kf = k+1 = 2.8e-5. But kb (k-3) is .01 * k-1 from Fay. Scaling by .01, kb = .01 * 10 = 0.1
fast: false
reversible: true

444474
type: KineticLaw
local parameters: 449130
local parameters: 449127
notes: kf*Glu*Gq_slash_Rec_minus_Gq-kb*Gq_slash_Rec_minus_Glu_minus_Gq

449130
type: LocalParameter
units: 443196
value: 1.5E-16

449127
type: LocalParameter
units: 443280
value: 2.520045E-14

444461
type: SpeciesReference
stoichiometry: 1.0
species: 419206

444448
type: SpeciesReference
stoichiometry: 1.0
species: 419186

419186
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

444435
type: SpeciesReference
stoichiometry: 1.0
species: 422106

422106
type: Species
notes: Varying the amount of (steady state) glu between .01 uM and up, the final amount of G*GTP complex does not change much. This means that the system should be reasonably robust wr to the amount of glu in the synaptic cleft. It would be nice to know how fast it is removed.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

425225
type: Reaction
kinetic law: 450556
product: 450544
reactant: 450532
reactant: 450520
fast: false
reversible: true

450556
type: KineticLaw
local parameters: 449470
local parameters: 449469
notes: k1*CaMKII_slash_CaMKII_minus_CaM*CaMKII_slash_tot_autonomous_CaMKII-k2*CaMKII_slash_tot_autonomous_CaMKII_slash_auton_286_slash_auton_286_cplx

449470
type: LocalParameter
units: 443196
value: 3.0E-15

449469
type: LocalParameter
units: 443280
value: 2.142855E-17

450544
type: SpeciesReference
stoichiometry: 1.0
species: 420526

420526
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

450532
type: SpeciesReference
stoichiometry: 1.0
species: 422286

422286
type: Species
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

450520
type: SpeciesReference
stoichiometry: 1.0
species: 420366

422965
type: Reaction
kinetic law: 444842
product: 444830
reactant: 444818
notes: Assume a reasonably good rate for dephosphorylating it, 1/sec
fast: false
reversible: true

444842
type: KineticLaw
local parameters: 449162
local parameters: 449159
notes: kf*Ras_slash_GAP_star_-kb*Ras_slash_GAP

449162
type: LocalParameter
units: 443196
value: 0.0

449159
type: LocalParameter
units: 443196
value: 1.5E-16

444830
type: SpeciesReference
stoichiometry: 1.0
species: 419786

444818
type: SpeciesReference
stoichiometry: 1.0
species: 419766

419766
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

424165
type: Reaction
kinetic law: 447557
product: 447545
product: 447533
reactant: 447521
fast: false
reversible: false

447557
type: KineticLaw
local parameters: 449377
notes: k3*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx

449377
type: LocalParameter
units: 443196
value: 1.5E-14

447545
type: SpeciesReference
stoichiometry: 1.0
species: 418846

447533
type: SpeciesReference
stoichiometry: 1.0
species: 418826

418826
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

447521
type: SpeciesReference
stoichiometry: 1.0
species: 418866

425425
type: Reaction
kinetic law: 451042
product: 451030
reactant: 451018
reactant: 451006
fast: false
reversible: true

451042
type: KineticLaw
local parameters: 449488
local parameters: 449487
notes: k1*CaMKII_slash_CaMKII_minus_thr286*PP1_minus_active-k2*PP1_minus_active_slash_Deph_thr286b_slash_Deph_thr286b_cplx

449488
type: LocalParameter
units: 443196
value: 2.1E-15

449487
type: LocalParameter
units: 443280
value: 5.147955E-16

451030
type: SpeciesReference
stoichiometry: 1.0
species: 420646

451018
type: SpeciesReference
stoichiometry: 1.0
species: 420546

451006
type: SpeciesReference
stoichiometry: 1.0
species: 420426

420906
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.12
initial amount: NaN
in compartment: 418386

422925
type: Reaction
kinetic law: 444770
product: 444758
reactant: 444746
fast: false
reversible: true

444770
type: KineticLaw
local parameters: 449154
local parameters: 449151
notes: kf*Ras_slash_GEF_star_-kb*Ras_slash_inact_minus_GEF

449154
type: LocalParameter
units: 443196
value: 0.0

449151
type: LocalParameter
units: 443196
value: 1.5E-15

444758
type: SpeciesReference
stoichiometry: 1.0
species: 419666

444746
type: SpeciesReference
stoichiometry: 1.0
species: 419686

419686
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

423526
type: Reaction
kinetic law: 446106
product: 446094
reactant: 446081
reactant: 446069
notes: Hasler et al FASEB J 6:2734-2741 1992 say Kd =1e-7M for type II, 5.6e-8 M for type I. Take mean which comes to 2e-13 #/cell Smith et al PNAS USA 78:3 1591-1595 1981 have better data. First kf/kb=2.1e7/M = 3.5e-5 (#/cell). Ogreid and Doskeland Febs Lett 129:2 287-292 1981 have figs suggesting time course of complete assoc is < 1 min.
fast: false
reversible: true

446106
type: KineticLaw
local parameters: 449274
local parameters: 449271
notes: kf*PKA_slash_R2C2*cAMP-kb*PKA_slash_R2C2_minus_cAMP

449274
type: LocalParameter
units: 443196
value: 4.95E-14

449271
type: LocalParameter
units: 443280
value: 8.1E-14

446094
type: SpeciesReference
stoichiometry: 1.0
species: 421126

446081
type: SpeciesReference
stoichiometry: 1.0
species: 421286

446069
type: SpeciesReference
stoichiometry: 1.0
species: 421106

421106
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 418386

422785
type: Reaction
kinetic law: 444422
product: 444409
reactant: 444396
reactant: 444383
notes: This is the k1-k2 equivalent for enzyme complex formation in the binding of Rec-Glu to Gq. See Fay et al Biochem 30 5066-5075 1991. kf = 5e-5 which is nearly the same as calculated by Fay et al. (4.67e-5) kb = .04 June 1996: Closer reading of Fay et al suggests that kb <= 0.0001, so kf = 1e-8 by detailed balance. This reaction appears to be neglible.
fast: false
reversible: true

444422
type: KineticLaw
local parameters: 449126
local parameters: 449123
notes: kf*Gq_slash_G_minus_GDP*Gq_slash_Rec_minus_Glu-kb*Gq_slash_Rec_minus_Glu_minus_Gq

449126
type: LocalParameter
units: 443196
value: 1.5E-19

449123
type: LocalParameter
units: 443280
value: 9.000045E-18

444409
type: SpeciesReference
stoichiometry: 1.0
species: 419206

444396
type: SpeciesReference
stoichiometry: 1.0
species: 419166

444383
type: SpeciesReference
stoichiometry: 1.0
species: 419126

422185
type: Species
notes: I am implementing this as acting only on the Rec-Gq complex, based on a more complete model PLC_Gq48.g which showed that the binding to the rec alone contributed only a small amount.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

424525
type: Reaction
kinetic law: 448448
product: 448436
product: 448424
reactant: 448412
fast: false
reversible: false

449407
type: LocalParameter
units: 443196
value: 9.0E-15

448436
type: SpeciesReference
stoichiometry: 1.0
species: 419506

448424
type: SpeciesReference
stoichiometry: 1.0
species: 419246

448412
type: SpeciesReference
stoichiometry: 1.0
species: 419526

419526
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

423005
type: Reaction
kinetic law: 444926
product: 444914
reactant: 444902
fast: false
reversible: true

444926
type: KineticLaw
local parameters: 449170
local parameters: 449167
notes: kf*Ras_slash_inact_minus_GEF_star_-kb*Ras_slash_inact_minus_GEF

449170
type: LocalParameter
units: 443196
value: 0.0

449167
type: LocalParameter
units: 443196
value: 1.5E-15

444914
type: SpeciesReference
stoichiometry: 1.0
species: 419666

444902
type: SpeciesReference
stoichiometry: 1.0
species: 419826

425725
type: Reaction
kinetic law: 451772
modifier: 451760
product: 451748
reactant: 451736
notes: Reduced Km to match expt data for basal activation of AC2 by PKC. Now k1 = 2.9e-6, k2 = 72, k3 = 18
fast: false
reversible: false

451772
type: KineticLaw
local parameters: 449517
local parameters: 449516
notes: kcat*AC_slash_AC2_star_*AC_slash_ATP/(Km+AC_slash_ATP)

449517
type: LocalParameter
units: 443160
value: 20.1152893440692

449516
type: LocalParameter
units: 443196
value: 1.05E-14

451748
type: SpeciesReference
stoichiometry: 1.0
species: 421286

451736
type: SpeciesReference
stoichiometry: 1.0
species: 422205

423885
type: Reaction
kinetic law: 446901
product: 446889
reactant: 446877
reactant: 446865
fast: false
reversible: true

446901
type: KineticLaw
local parameters: 449346
local parameters: 449343
notes: kf*PKM_slash_Ca_detector*Ca^2-kb*PKM_slash_Ca_dot_detector_complex

449346
type: LocalParameter
units: 443196
value: 6.0E-16

449343
type: LocalParameter
units: 443232
value: 1.500039E-16

446889
type: SpeciesReference
stoichiometry: 1.0
species: 422006

446877
type: SpeciesReference
stoichiometry: 2.0
species: 421646

446865
type: SpeciesReference
stoichiometry: 1.0
species: 421946

421946
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 418386

424705
type: Reaction
kinetic law: 448883
product: 448871
reactant: 448859
reactant: 448847
notes: Kinetics same as GEF-bg-act-ras
fast: false
reversible: true

448883
type: KineticLaw
local parameters: 449424
local parameters: 449423
notes: k1*Ras_slash_GDP_minus_Ras*Ras_slash_GEF_star_-k2*Ras_slash_GEF_star__slash_GEF_star__minus_act_minus_ras_slash_GEF_star__minus_act_minus_ras_cplx

449424
type: LocalParameter
units: 443196
value: 1.2E-16

449423
type: LocalParameter
units: 443280
value: 2.97E-16

448871
type: SpeciesReference
stoichiometry: 1.0
species: 419706

419706
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

448859
type: SpeciesReference
stoichiometry: 1.0
species: 419686

448847
type: SpeciesReference
stoichiometry: 1.0
species: 419746

418986
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

425985
type: Reaction
kinetic law: 452400
product: 452388
product: 452376
reactant: 452364
fast: false
reversible: false

452400
type: KineticLaw
local parameters: 449546
notes: k3*MKP3_slash_nuc_MAPK_star__slash_act_transcription_slash_act_transcription_cplx

449546
type: LocalParameter
units: 443196
value: 6.0E-18

452388
type: SpeciesReference
stoichiometry: 1.0
species: 421686

452376
type: SpeciesReference
stoichiometry: 1.0
species: 421786

452364
type: SpeciesReference
stoichiometry: 1.0
species: 421706

421226
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

425045
type: Reaction
kinetic law: 450095
product: 450083
product: 450071
reactant: 450059
fast: false
reversible: false

450095
type: KineticLaw
local parameters: 449455
notes: k3*EGFR_slash_L_dot_EGFR_slash_phosph_Shc_slash_phosph_Shc_cplx

449455
type: LocalParameter
units: 443196
value: 3.0E-16

450083
type: SpeciesReference
stoichiometry: 1.0
species: 420046

450071
type: SpeciesReference
stoichiometry: 1.0
species: 420126

450059
type: SpeciesReference
stoichiometry: 1.0
species: 420086

424385
type: Reaction
kinetic law: 448112
product: 448100
reactant: 448088
reactant: 448076
notes: Rate consts same as for MAPKKtyr.
fast: false
reversible: true

448112
type: KineticLaw
local parameters: 449397
local parameters: 449396
notes: k1*MAPK_slash_MAPK_minus_tyr*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx

449397
type: LocalParameter
units: 443196
value: 1.8E-15

449396
type: LocalParameter
units: 443280
value: 4.86E-14

448100
type: SpeciesReference
stoichiometry: 1.0
species: 419406

448088
type: SpeciesReference
stoichiometry: 1.0
species: 419366

448076
type: SpeciesReference
stoichiometry: 1.0
species: 419346

424325
type: Reaction
kinetic law: 447968
product: 447956
product: 447944
product: 447932
reactant: 447920
fast: false
reversible: false

447968
type: KineticLaw
local parameters: 449389
notes: k3*PLCbeta_slash_PLC_minus_Ca_minus_Gq_slash_PLCb_minus_Ca_minus_Gq_slash_PLCb_minus_Ca_minus_Gq_cplx

449389
type: LocalParameter
units: 443196
value: 7.2E-14

447956
type: SpeciesReference
stoichiometry: 1.0
species: 419006

447944
type: SpeciesReference
stoichiometry: 1.0
species: 418926

447932
type: SpeciesReference
stoichiometry: 1.0
species: 418566

447920
type: SpeciesReference
stoichiometry: 1.0
species: 419026

420006
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

425665
type: Reaction
kinetic law: 451627
product: 451615
reactant: 451602
reactant: 451589
notes: The rates here are so slow I do not know if we should even bother with this enz reacn. These numbers are from Liu and Storm. Other refs suggest that the Km stays the same but the Vmax goes to 10% of the CaM stim levels. Prev: k1=2.2e-9, k2 = 0.0052, k3 = 0.0013 New : k1=5.7e-8, k2=.136, k3=.034
fast: false
reversible: true

451627
type: KineticLaw
local parameters: 449512
local parameters: 449509
notes: k1*PP1_slash_I1_star_*CaNAB_minus_Ca4-k2*CaNAB_minus_Ca4_slash_dephosph_inhib1_noCaM_slash_dephosph_inhib1_noCaM_cplx

449512
type: LocalParameter
units: 443196
value: 2.04E-16

449509
type: LocalParameter
units: 443280
value: 5.13E-17

451615
type: SpeciesReference
stoichiometry: 1.0
species: 420986

420986
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

451602
type: SpeciesReference
stoichiometry: 1.0
species: 420966

420966
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

451589
type: SpeciesReference
stoichiometry: 1.0
species: 420846

424965
type: Reaction
kinetic law: 449903
product: 449891
product: 449879
reactant: 449866
fast: false
reversible: false

449903
type: KineticLaw
local parameters: 449449
notes: k3*Shc_star__dot_Sos_dot_Grb2_slash_Sos_dot_Ras_GEF_slash_Sos_dot_Ras_GEF_cplx

449449
type: LocalParameter
units: 443196
value: 3.0E-17

449891
type: SpeciesReference
stoichiometry: 1.0
species: 419986

449879
type: SpeciesReference
stoichiometry: 1.0
species: 419726

449866
type: SpeciesReference
stoichiometry: 1.0
species: 420006

425945
type: Reaction
kinetic law: 452304
product: 452292
product: 452280
reactant: 452268
fast: false
reversible: false

452304
type: KineticLaw
local parameters: 449543
notes: k3*AC_slash_CaM_dot_PDE1_slash_CaM_dot_PDE1_slash_CaM_dot_PDE1_cplx

449543
type: LocalParameter
units: 443196
value: 1.5E-14

452292
type: SpeciesReference
stoichiometry: 1.0
species: 421586

452280
type: SpeciesReference
stoichiometry: 1.0
species: 421426

452268
type: SpeciesReference
stoichiometry: 1.0
species: 421606

423305
type: Reaction
kinetic law: 445588
product: 445576
reactant: 445564
reactant: 445552
notes: K3 = 21.5, K4 = 2.8. Assuming that the K4 step happens first, we get kb/kf = 2.8 uM = 1.68e6 so kf =6e-6 assuming kb = 10
fast: false
reversible: true

445588
type: KineticLaw
local parameters: 449230
local parameters: 449227
notes: kf*CaM_minus_TR2_minus_Ca2*Ca-kb*CaM_minus_Ca3

449230
type: LocalParameter
units: 443196
value: 1.5E-14

449227
type: LocalParameter
units: 443280
value: 5.4E-15

445576
type: SpeciesReference
stoichiometry: 1.0
species: 420746

445564
type: SpeciesReference
stoichiometry: 1.0
species: 421646

445552
type: SpeciesReference
stoichiometry: 1.0
species: 420766

420266
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.82
initial amount: NaN
in compartment: 418386

422585
type: Reaction
kinetic law: 443958
product: 443946
reactant: 443934
notes: The enzyme is IP3 5-phosphomonesterase. about 45K. Actual products are Ins(1,4)P2, and cIns(1:2,4,5)P3. review in Majerus et al Science 234 1519-1526, 1986. Meyer and Stryer 1988 PNAS 85:5051-5055 est decay of IP3 at 1-3/sec
fast: false
reversible: true

443958
type: KineticLaw
local parameters: 449086
local parameters: 449083
notes: kf*IP3-kb*PLCbeta_slash_Inositol

449086
type: LocalParameter
units: 443196
value: 0.0

449083
type: LocalParameter
units: 443196
value: 3.75E-15

443946
type: SpeciesReference
stoichiometry: 1.0
species: 422126

443934
type: SpeciesReference
stoichiometry: 1.0
species: 418926

423805
type: Reaction
kinetic law: 446745
product: 446733
reactant: 446721
fast: false
reversible: true

446745
type: KineticLaw
local parameters: 449330
local parameters: 449327
notes: kf*Ca_input-kb*Ca

449330
type: LocalParameter
units: 443196
value: 1.5E-13

449327
type: LocalParameter
units: 443196
value: 1.5E-13

446733
type: SpeciesReference
stoichiometry: 1.0
species: 421646

446721
type: SpeciesReference
stoichiometry: 1.0
species: 421666

421666
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.08
initial amount: NaN
in compartment: 418386

424925
type: Reaction
kinetic law: 449806
product: 449794
product: 449782
reactant: 449770
fast: false
reversible: false

449806
type: KineticLaw
local parameters: 449443
notes: k3*PKA_minus_active_slash_phosph_minus_PDE_slash_phosph_minus_PDE_cplx

449443
type: LocalParameter
units: 443196
value: 1.35E-14

449794
type: SpeciesReference
stoichiometry: 1.0
species: 419886

449782
type: SpeciesReference
stoichiometry: 1.0
species: 421506

449770
type: SpeciesReference
stoichiometry: 1.0
species: 419946

419946
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

426305
type: Reaction
kinetic law: 453183
product: 453171
product: 453159
product: 453147
reactant: 453135
fast: false
reversible: false

453183
type: KineticLaw
local parameters: 449576
notes: k3*PKC_minus_active_slash_PKC_minus_phosph_minus_ng_minus_CaM_slash_PKC_minus_phosph_minus_ng_minus_CaM_cplx

449576
type: LocalParameter
units: 443196
value: 5.25E-16

453171
type: SpeciesReference
stoichiometry: 1.0
species: 422325

453159
type: SpeciesReference
stoichiometry: 1.0
species: 420706

453147
type: SpeciesReference
stoichiometry: 1.0
species: 420666

453135
type: SpeciesReference
stoichiometry: 1.0
species: 421906

424785
type: Reaction
kinetic law: 449272
product: 449260
reactant: 449248
reactant: 449236
notes: Kinetics same as GEF-bg_act-ras
fast: false
reversible: true

449272
type: KineticLaw
local parameters: 449433
local parameters: 449432
notes: k1*Ras_slash_GDP_minus_Ras*Ras_slash_CaM_minus_GEF-k2*Ras_slash_CaM_minus_GEF_slash_CaM_minus_GEF_minus_act_minus_ras_slash_CaM_minus_GEF_minus_act_minus_ras_cplx

449433
type: LocalParameter
units: 443196
value: 1.2E-16

449432
type: LocalParameter
units: 443280
value: 2.97E-16

449260
type: SpeciesReference
stoichiometry: 1.0
species: 419866

419866
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

449248
type: SpeciesReference
stoichiometry: 1.0
species: 419846

449236
type: SpeciesReference
stoichiometry: 1.0
species: 419746

424185
type: Reaction
kinetic law: 447605
product: 447593
reactant: 447581
reactant: 447569
notes: Ueki et al JBC 269(22):15756-15761 show the presence of this step, but not the rate consts, which are derived from Sanghera et al JBC 265(1):52-57, 1990, see the deriv in the MAPK* notes.
fast: false
reversible: true

447605
type: KineticLaw
local parameters: 449379
local parameters: 449378
notes: k1*MAPK_slash_craf_minus_1_star_*MAPK_star_-k2*MAPK_star__slash_MAPK_star__minus_feedback_slash_MAPK_star__minus_feedback_cplx

449379
type: LocalParameter
units: 443196
value: 6.0E-14

449378
type: LocalParameter
units: 443280
value: 2.925045E-15

447593
type: SpeciesReference
stoichiometry: 1.0
species: 418886

418886
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

447581
type: SpeciesReference
stoichiometry: 1.0
species: 418846

447569
type: SpeciesReference
stoichiometry: 1.0
species: 419266

419266
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

423565
type: Reaction
kinetic law: 446202
product: 446190
reactant: 446178
reactant: 446166
fast: false
reversible: true

446202
type: KineticLaw
local parameters: 449282
local parameters: 449279
notes: kf*PKA_slash_R2C2_minus_cAMP2*cAMP-kb*PKA_slash_R2C2_minus_cAMP3

449282
type: LocalParameter
units: 443196
value: 1.65E-13

449279
type: LocalParameter
units: 443280
value: 1.1249955E-13

446190
type: SpeciesReference
stoichiometry: 1.0
species: 421166

421166
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

446178
type: SpeciesReference
stoichiometry: 1.0
species: 421286

446166
type: SpeciesReference
stoichiometry: 1.0
species: 421146

423725
type: Reaction
kinetic law: 446576
product: 446563
reactant: 446551
reactant: 446539
notes: Half-max 8nM from Tang et al JBC266:13 8595-8603 kb/kf = 8 nM = 4800#/cell so kf = kb * 2.08e-4
fast: false
reversible: true

446576
type: KineticLaw
local parameters: 449314
local parameters: 449311
notes: kf*Gs_minus_alpha*AC_slash_AC1-kb*AC_slash_AC1_minus_Gs

449314
type: LocalParameter
units: 443196
value: 1.5E-15

449311
type: LocalParameter
units: 443280
value: 1.89E-13

446563
type: SpeciesReference
stoichiometry: 1.0
species: 421406

446551
type: SpeciesReference
stoichiometry: 1.0
species: 421326

421326
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.02
initial amount: NaN
in compartment: 418386

446539
type: SpeciesReference
stoichiometry: 1.0
species: 421626

421046
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

425885
type: Reaction
kinetic law: 452158
product: 452146
reactant: 452134
reactant: 452122
notes: Rate is 1/6 of the CaM stim form. We\'ll just reduce all lf k1, k2, k3 so that the Vmax goes down 1/6.
fast: false
reversible: true

452158
type: KineticLaw
local parameters: 449539
local parameters: 449538
notes: k1*cAMP*AC_slash_PDE1-k2*AC_slash_PDE1_slash_PDE1_slash_PDE1_cplx

449539
type: LocalParameter
units: 443196
value: 1.0005E-14

449538
type: LocalParameter
units: 443280
value: 3.149955E-16

452146
type: SpeciesReference
stoichiometry: 1.0
species: 421566

452134
type: SpeciesReference
stoichiometry: 1.0
species: 421546

452122
type: SpeciesReference
stoichiometry: 1.0
species: 421286

423245
type: Reaction
kinetic law: 445456
product: 445444
reactant: 445432
reactant: 445420
notes: Affinity is up 1000X. Time to release is about 20 sec, so the kb is OK at 0.1 This makes Kf around 1.6666e-3
fast: false
reversible: true

445456
type: KineticLaw
local parameters: 449218
local parameters: 449215
notes: kf*CaMKII_slash_CaMKII_minus_thr286*CaM_minus_Ca4-kb*CaMKII_slash_CaMKII_minus_thr286_star__minus_CaM

449218
type: LocalParameter
units: 443196
value: 1.5E-16

449215
type: LocalParameter
units: 443280
value: 1.500255E-12

445444
type: SpeciesReference
stoichiometry: 1.0
species: 420386

420386
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

445432
type: SpeciesReference
stoichiometry: 1.0
species: 419966

445420
type: SpeciesReference
stoichiometry: 1.0
species: 420426

421066
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

418446
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.38955555555556E-17
initial amount: NaN
in compartment: 418386

423985
type: Reaction
kinetic law: 447120
product: 447108
reactant: 447096
reactant: 447084
notes: 10 X raise oct 22 12 X further raise oct 24 to allow for correct conc of enzyme
fast: false
reversible: true

447120
type: KineticLaw
local parameters: 449361
local parameters: 449360
notes: k1*PLA2_slash_APC*PLA2_slash_PIP2_minus_PLA2_star_-k2*PLA2_slash_PIP2_minus_PLA2_star__slash_kenz_slash_kenz_cplx

449361
type: LocalParameter
units: 443196
value: 6.624E-14

449360
type: LocalParameter
units: 443280
value: 4.140045E-15

447108
type: SpeciesReference
stoichiometry: 1.0
species: 418686

447096
type: SpeciesReference
stoichiometry: 1.0
species: 418666

447084
type: SpeciesReference
stoichiometry: 1.0
species: 422066

420406
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

424085
type: Reaction
kinetic law: 447364
product: 447352
product: 447340
reactant: 447328
fast: false
reversible: false

447364
type: KineticLaw
local parameters: 449368
notes: k3*PLA2_slash_DAG_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx

449368
type: LocalParameter
units: 443196
value: 9.0E-14

447352
type: SpeciesReference
stoichiometry: 1.0
species: 418746

447340
type: SpeciesReference
stoichiometry: 1.0
species: 418586

447328
type: SpeciesReference
stoichiometry: 1.0
species: 418766

425305
type: Reaction
kinetic law: 450750
product: 450738
reactant: 450726
reactant: 450714
fast: false
reversible: true

450750
type: KineticLaw
local parameters: 449479
local parameters: 449478
notes: k1*CaMKII_slash_CaMKII_star__star__star_*PP1_minus_active-k2*PP1_minus_active_slash_Deph_minus_thr305_slash_Deph_minus_thr305_cplx

449479
type: LocalParameter
units: 443196
value: 2.1E-15

449478
type: LocalParameter
units: 443280
value: 5.147955E-16

450738
type: SpeciesReference
stoichiometry: 1.0
species: 420586

450726
type: SpeciesReference
stoichiometry: 1.0
species: 420546

450714
type: SpeciesReference
stoichiometry: 1.0
species: 420406

420806
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

423945
type: Reaction
kinetic law: 447024
product: 447011
reactant: 446998
reactant: 446985
notes: 10 x raise oct22 12 x oct 24, set k2 = 4 * k3
fast: false
reversible: true

447024
type: KineticLaw
local parameters: 449358
local parameters: 449355
notes: k1*PLA2_slash_APC*PLA2_slash_PLA2_minus_Ca_star_-k2*PLA2_slash_PLA2_minus_Ca_star__slash_kenz_slash_kenz_cplx

449358
type: LocalParameter
units: 443196
value: 3.24E-14

449355
type: LocalParameter
units: 443280
value: 2.025E-15

447011
type: SpeciesReference
stoichiometry: 1.0
species: 418646

418646
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

446998
type: SpeciesReference
stoichiometry: 1.0
species: 418626

418626
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

446985
type: SpeciesReference
stoichiometry: 1.0
species: 422066

424265
type: Reaction
kinetic law: 447798
product: 447786
reactant: 447774
reactant: 447762
notes: From Sternweis et al Phil Trans R Soc Lond 1992, also matched by Homma et al. k1 = 1.5e-5, now 4.2e-6 k2 = 70/sec; now 40/sec k3 = 17.5/sec; now 10/sec Note that the wording in Sternweis et al is ambiguous re the Km.
fast: false
reversible: true

447798
type: KineticLaw
local parameters: 449385
local parameters: 449384
notes: k1*PIP2*PLCbeta_slash_PLC_minus_Ca-k2*PLCbeta_slash_PLC_minus_Ca_slash_PLC_minus_Ca_slash_PLC_minus_Ca_cplx

449385
type: LocalParameter
units: 443196
value: 6.0E-14

449384
type: LocalParameter
units: 443280
value: 3.78E-15

447786
type: SpeciesReference
stoichiometry: 1.0
species: 418986

447774
type: SpeciesReference
stoichiometry: 1.0
species: 418966

447762
type: SpeciesReference
stoichiometry: 1.0
species: 422166

423765
type: Reaction
kinetic law: 446660
product: 446648
reactant: 446636
notes: The rates for this are poorly constrained. In adipocytes (probably a different PDE) the dephosphorylation is complete within 15 min, but there are no intermediate time points so it could be much faster. Identity of phosphatase etc is still unknown.
fast: false
reversible: true

446660
type: KineticLaw
local parameters: 449322
local parameters: 449319
notes: kf*AC_slash_cAMP_minus_PDE_star_-kb*AC_slash_cAMP_minus_PDE

449322
type: LocalParameter
units: 443196
value: 0.0

449319
type: LocalParameter
units: 443196
value: 1.5E-16

446648
type: SpeciesReference
stoichiometry: 1.0
species: 421466

421466
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.45
initial amount: NaN
in compartment: 418386

446636
type: SpeciesReference
stoichiometry: 1.0
species: 421506

423465
type: Reaction
kinetic law: 445961
product: 445949
reactant: 445937
reactant: 445925
notes: Disabled. See notes for PP2B7.g
fast: false
reversible: true

445961
type: KineticLaw
local parameters: 449262
local parameters: 449259
notes: kf*CaNAB_minus_Ca4*CaM_minus_TR2_minus_Ca2-kb*PP2B_slash_CaMCa2_minus_CANAB

449262
type: LocalParameter
units: 443196
value: 1.5E-15

449259
type: LocalParameter
units: 443280
value: 3.600045E-16

445949
type: SpeciesReference
stoichiometry: 1.0
species: 421066

445937
type: SpeciesReference
stoichiometry: 1.0
species: 420766

445925
type: SpeciesReference
stoichiometry: 1.0
species: 420966

425805
type: Reaction
kinetic law: 451965
product: 451953
reactant: 451941
reactant: 451929
notes: Best rates are from Conti et al Biochem 34 7979-7987 1995. Though these are for the Sertoli cell form, it looks like they carry nicely into alternatively spliced brain form. See Sette et al JBC 269:28 18271-18274 Km ~2 uM, Vmax est ~ 10 umol/min/mg for pure form. Brain protein is 93 kD but this was 67. So k3 ~10, k2 ~40, k1 ~4.2e-6
fast: false
reversible: true

451965
type: KineticLaw
local parameters: 449533
local parameters: 449530
notes: k1*cAMP*AC_slash_cAMP_minus_PDE-k2*AC_slash_cAMP_minus_PDE_slash_PDE_slash_PDE_cplx

449533
type: LocalParameter
units: 443196
value: 6.0E-14

449530
type: LocalParameter
units: 443280
value: 3.78E-15

451953
type: SpeciesReference
stoichiometry: 1.0
species: 421486

451941
type: SpeciesReference
stoichiometry: 1.0
species: 421466

451929
type: SpeciesReference
stoichiometry: 1.0
species: 421286

425165
type: Reaction
kinetic law: 450412
product: 450400
product: 450388
reactant: 450376
fast: false
reversible: false

450412
type: KineticLaw
local parameters: 449465
notes: k3*CaMKII_slash_tot_CaM_CaMKII_slash_CaM_act_286_slash_CaM_act_286_cplx

449465
type: LocalParameter
units: 443196
value: 7.5E-16

450400
type: SpeciesReference
stoichiometry: 1.0
species: 422285

450388
type: SpeciesReference
stoichiometry: 1.0
species: 420386

450376
type: SpeciesReference
stoichiometry: 1.0
species: 420486

424126
type: Reaction
kinetic law: 447461
product: 447449
product: 447436
reactant: 447424
fast: false
reversible: false

447461
type: KineticLaw
local parameters: 449371
notes: k3*PLA2_slash_PLA2_star__minus_Ca_slash_kenz_slash_kenz_cplx

449371
type: LocalParameter
units: 443196
value: 1.8E-13

447449
type: SpeciesReference
stoichiometry: 1.0
species: 418786

447436
type: SpeciesReference
stoichiometry: 1.0
species: 418586

447424
type: SpeciesReference
stoichiometry: 1.0
species: 418806

418806
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

424945
type: Reaction
kinetic law: 449854
product: 449842
reactant: 449830
reactant: 449818
fast: false
reversible: true

449854
type: KineticLaw
local parameters: 449448
local parameters: 449445
notes: k1*Ras_slash_GDP_minus_Ras*Shc_star__dot_Sos_dot_Grb2-k2*Shc_star__dot_Sos_dot_Grb2_slash_Sos_dot_Ras_GEF_slash_Sos_dot_Ras_GEF_cplx

449448
type: LocalParameter
units: 443196
value: 1.2E-16

449445
type: LocalParameter
units: 443280
value: 2.97E-16

449842
type: SpeciesReference
stoichiometry: 1.0
species: 420006

449830
type: SpeciesReference
stoichiometry: 1.0
species: 419986

449818
type: SpeciesReference
stoichiometry: 1.0
species: 419746

422406
type: Reaction
kinetic law: 443474
product: 443462
reactant: 443449
fast: false
reversible: true

443474
type: KineticLaw
local parameters: 449042
local parameters: 449039
notes: kf*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_memb_star_

449042
type: LocalParameter
units: 443196
value: 5.2539E-15

449039
type: LocalParameter
units: 443196
value: 1.90575E-15

443462
type: SpeciesReference
stoichiometry: 1.0
species: 418446

443449
type: SpeciesReference
stoichiometry: 1.0
species: 418426

422545
type: Reaction
kinetic law: 443838
product: 443826
reactant: 443814
reactant: 443802
notes: To start off, same kinetics as the PLA2-Ca-act direct pathway. Oops ! Missed out the Ca input to this pathway first time round. Let\'s raise the forward rate about 3x to 5e-6. This will let us reduce the rather high rates we have used for the kenz on PLA2*-Ca. In fact, it may be that the rates are not that different, just that this pathway for getting the PLA2 to the memb is more efficien....
fast: false
reversible: true

443838
type: KineticLaw
local parameters: 449074
local parameters: 449071
notes: kf*PLA2_slash_PLA2_star_*Ca-kb*PLA2_slash_PLA2_star__minus_Ca

449074
type: LocalParameter
units: 443196
value: 1.5E-16

449071
type: LocalParameter
units: 443280
value: 9.000045E-15

443826
type: SpeciesReference
stoichiometry: 1.0
species: 418786

443814
type: SpeciesReference
stoichiometry: 1.0
species: 421646

443802
type: SpeciesReference
stoichiometry: 1.0
species: 418826

426065
type: Reaction
kinetic law: 452593
product: 452581
product: 452569
reactant: 452557
fast: false
reversible: false

452593
type: KineticLaw
local parameters: 449555
notes: k3*MKP3_slash_MKP_minus_3_slash_MKP3_minus_tyr_minus_deph_slash_MKP3_minus_tyr_minus_deph_cplx

449555
type: LocalParameter
units: 443196
value: 6.0E-15

452581
type: SpeciesReference
stoichiometry: 1.0
species: 421726

452569
type: SpeciesReference
stoichiometry: 1.0
species: 419306

419306
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.6
initial amount: NaN
in compartment: 418386

452557
type: SpeciesReference
stoichiometry: 1.0
species: 421766

423745
type: Reaction
kinetic law: 446624
product: 446612
reactant: 446600
reactant: 446588
notes: kb/kf = 1.2 nM so kf = kb/720 = 1.3888 * kb.
fast: false
reversible: true

446624
type: KineticLaw
local parameters: 449318
local parameters: 449315
notes: kf*Gs_minus_alpha*AC_slash_AC2_star_-kb*AC_slash_AC2_star__minus_Gs

449318
type: LocalParameter
units: 443196
value: 1.5E-15

449315
type: LocalParameter
units: 443280
value: 1.2499245E-12

446612
type: SpeciesReference
stoichiometry: 1.0
species: 421446

446600
type: SpeciesReference
stoichiometry: 1.0
species: 421346

446588
type: SpeciesReference
stoichiometry: 1.0
species: 421626

425385
type: Reaction
kinetic law: 450945
product: 450933
reactant: 450921
reactant: 450909
fast: false
reversible: true

450945
type: KineticLaw
local parameters: 449485
local parameters: 449484
notes: k1*CaMKII_slash_CaMKII_star__star__star_*PP1_minus_active-k2*PP1_minus_active_slash_Deph_minus_thr286c_slash_Deph_minus_thr286c_cplx

449485
type: LocalParameter
units: 443196
value: 2.1E-15

449484
type: LocalParameter
units: 443280
value: 5.147955E-16

450933
type: SpeciesReference
stoichiometry: 1.0
species: 420626

450921
type: SpeciesReference
stoichiometry: 1.0
species: 420546

450909
type: SpeciesReference
stoichiometry: 1.0
species: 420406

422485
type: Reaction
kinetic law: 443704
product: 443691
reactant: 443679
reactant: 443667
fast: false
reversible: true

443704
type: KineticLaw
local parameters: 449062
local parameters: 449059
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star_

449062
type: LocalParameter
units: 443196
value: 1.5E-16

449059
type: LocalParameter
units: 443280
value: 1.799955E-17

443691
type: SpeciesReference
stoichiometry: 1.0
species: 418706

418706
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

443679
type: SpeciesReference
stoichiometry: 1.0
species: 418626

443667
type: SpeciesReference
stoichiometry: 1.0
species: 422086

426285
type: Reaction
kinetic law: 453123
product: 453111
reactant: 453099
reactant: 453087
notes: Rates are 60% those of PKC-phosph-neurogranin. See Huang et al ABB 305:2 570-580 1993
fast: false
reversible: true

453123
type: KineticLaw
local parameters: 449575
local parameters: 449574
notes: k1*CaM_slash_neurogranin_minus_CaM*PKC_minus_active-k2*PKC_minus_active_slash_PKC_minus_phosph_minus_ng_minus_CaM_slash_PKC_minus_phosph_minus_ng_minus_CaM_cplx

449575
type: LocalParameter
units: 443196
value: 2.1E-15

449574
type: LocalParameter
units: 443280
value: 9.18E-17

453111
type: SpeciesReference
stoichiometry: 1.0
species: 421906

453099
type: SpeciesReference
stoichiometry: 1.0
species: 422325

453087
type: SpeciesReference
stoichiometry: 1.0
species: 420686

425245
type: Reaction
kinetic law: 450606
product: 450593
product: 450580
reactant: 450568
fast: false
reversible: false

450606
type: KineticLaw
local parameters: 449471
notes: k3*CaMKII_slash_tot_autonomous_CaMKII_slash_auton_286_slash_auton_286_cplx

449471
type: LocalParameter
units: 443196
value: 7.5E-16

450593
type: SpeciesReference
stoichiometry: 1.0
species: 422286

450580
type: SpeciesReference
stoichiometry: 1.0
species: 420386

450568
type: SpeciesReference
stoichiometry: 1.0
species: 420526

422445
type: Reaction
kinetic law: 443607
product: 443595
reactant: 443583
reactant: 443571
notes: Leslie and Channon BBA 1045 (1990) 261-270 fig6 pp267.
fast: false
reversible: true

443607
type: KineticLaw
local parameters: 449054
local parameters: 449051
notes: kf*PLA2_slash_PLA2_minus_cytosolic*Ca-kb*PLA2_slash_PLA2_minus_Ca_star_

449054
type: LocalParameter
units: 443196
value: 1.5E-16

449051
type: LocalParameter
units: 443280
value: 1.499985E-15

443595
type: SpeciesReference
stoichiometry: 1.0
species: 418626

443583
type: SpeciesReference
stoichiometry: 1.0
species: 421646

443571
type: SpeciesReference
stoichiometry: 1.0
species: 418606

422505
type: Reaction
kinetic law: 443754
product: 443742
reactant: 443729
reactant: 443716
notes: 27 June 1996 Scaled kf down by 0.015 from 3.33e-7 to 5e-9 to fit with revised DAG estimates and use of mole-fraction to calculate eff on PLA2.
fast: false
reversible: true

443754
type: KineticLaw
local parameters: 449066
local parameters: 449063
notes: kf*DAG*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_DAG_minus_Ca_minus_PLA2_star_

449066
type: LocalParameter
units: 443196
value: 6.0E-15

449063
type: LocalParameter
units: 443280
value: 4.499955E-18

443742
type: SpeciesReference
stoichiometry: 1.0
species: 418746

443729
type: SpeciesReference
stoichiometry: 1.0
species: 418626

443716
type: SpeciesReference
stoichiometry: 1.0
species: 418566

423165
type: Reaction
kinetic law: 445275
product: 445263
reactant: 445250
reactant: 445238
notes: Nice curves from Homma et al JBC 263:14 6592-6598 1988 Fig 5c. The activity falls above 10 uM, but that is too high to reach physiologically anyway, so we\'ll ignore the higher pts and match the lower ones only. Half-max at 1 uM. But Wahl et al JBC 267:15 10447-10456 1992 have half-max at 56 nM which is what I\'ll use.
fast: false
reversible: true

445275
type: KineticLaw
local parameters: 449202
local parameters: 449199
notes: kf*PLC_g_slash_PLC_g*Ca-kb*PLC_g_slash_Ca_dot_PLC_g

449202
type: LocalParameter
units: 443196
value: 1.5E-14

449199
type: LocalParameter
units: 443280
value: 2.7E-13

445263
type: SpeciesReference
stoichiometry: 1.0
species: 420306

420306
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

445250
type: SpeciesReference
stoichiometry: 1.0
species: 421646

445238
type: SpeciesReference
stoichiometry: 1.0
species: 420266

424545
type: Reaction
kinetic law: 448496
product: 448484
reactant: 448472
reactant: 448460
notes: See: Kyriakis et al Nature 358 pp 417-421 1992 Ahn et al Curr Op Cell Biol 4:992-999 1992 for this pathway. See parent PPhosphatase2A for parms.
fast: false
reversible: true

449412
type: LocalParameter
units: 443196
value: 3.6E-14

449409
type: LocalParameter
units: 443280
value: 2.87415E-15

448484
type: SpeciesReference
stoichiometry: 1.0
species: 419546

419546
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

448472
type: SpeciesReference
stoichiometry: 1.0
species: 419506

448460
type: SpeciesReference
stoichiometry: 1.0
species: 419366

424805
type: Reaction
kinetic law: 449321
product: 449308
product: 449296
reactant: 449284
fast: false
reversible: false

449321
type: KineticLaw
local parameters: 449434
notes: k3*Ras_slash_CaM_minus_GEF_slash_CaM_minus_GEF_minus_act_minus_ras_slash_CaM_minus_GEF_minus_act_minus_ras_cplx

449434
type: LocalParameter
units: 443196
value: 3.0E-17

449308
type: SpeciesReference
stoichiometry: 1.0
species: 419846

449296
type: SpeciesReference
stoichiometry: 1.0
species: 419726

449284
type: SpeciesReference
stoichiometry: 1.0
species: 419866

423965
type: Reaction
kinetic law: 447072
product: 447060
product: 447048
reactant: 447036
fast: false
reversible: false

447072
type: KineticLaw
local parameters: 449359
notes: k3*PLA2_slash_PLA2_minus_Ca_star__slash_kenz_slash_kenz_cplx

449359
type: LocalParameter
units: 443196
value: 8.1E-15

447060
type: SpeciesReference
stoichiometry: 1.0
species: 418626

447048
type: SpeciesReference
stoichiometry: 1.0
species: 418586

447036
type: SpeciesReference
stoichiometry: 1.0
species: 418646

424505
type: Reaction
kinetic law: 448400
product: 448388
reactant: 448376
reactant: 448364
notes: See parent PPhosphatase2A for parms
fast: false
reversible: true

449406
type: LocalParameter
units: 443196
value: 3.6E-14

449405
type: LocalParameter
units: 443280
value: 2.87415E-15

448388
type: SpeciesReference
stoichiometry: 1.0
species: 419526

448376
type: SpeciesReference
stoichiometry: 1.0
species: 419506

448364
type: SpeciesReference
stoichiometry: 1.0
species: 419266

419146
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.3
initial amount: NaN
in compartment: 418386

420066
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

425465
type: Reaction
kinetic law: 451138
product: 451126
reactant: 451114
reactant: 451102
notes: From Seki et al ABB 316(2):673-679
fast: false
reversible: true

451138
type: KineticLaw
local parameters: 449494
local parameters: 449491
notes: k1*CaM_slash_neurogranin_star_*CaM_po_Ca_pc_n_minus_CaNAB-k2*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_neurogranin_slash_dephosph_neurogranin_cplx

449494
type: LocalParameter
units: 443196
value: 4.005E-15

449491
type: LocalParameter
units: 443280
value: 5.004045E-16

451126
type: SpeciesReference
stoichiometry: 1.0
species: 420786

451114
type: SpeciesReference
stoichiometry: 1.0
species: 422305

451102
type: SpeciesReference
stoichiometry: 1.0
species: 420706

423485
type: Reaction
kinetic law: 446009
product: 445997
reactant: 445985
reactant: 445973
fast: false
reversible: true

446009
type: KineticLaw
local parameters: 449266
local parameters: 449263
notes: kf*CaM_minus_Ca3*CaNAB_minus_Ca4-kb*PP2B_slash_CaMCa3_minus_CaNAB

449266
type: LocalParameter
units: 443196
value: 1.5E-15

449263
type: LocalParameter
units: 443280
value: 3.357045E-15

445997
type: SpeciesReference
stoichiometry: 1.0
species: 421046

445985
type: SpeciesReference
stoichiometry: 1.0
species: 420966

445973
type: SpeciesReference
stoichiometry: 1.0
species: 420746

425065
type: Reaction
fast: false
kinetic law: 450157
modifier: 450145
reversible: false
product: 450120
product: 450132
reactant: 450107
notes: Mainly Homma et al JBC 263:14 1988 pp 6592, but these parms are the Ca-stimulated form. It is not clear whether the enzyme is activated by tyrosine phosphorylation at this point or not. Wahl et al JBC 267:15 10447-10456 1992 say that the Ca_stim and phosph form has 7X higher affinity for substrate than control. This is close to Wahl\'s figure 7, which I am using as reference.

450157
type: KineticLaw
local parameters: 449457
local parameters: 449456
notes: kcat*PLC_g_slash_Ca_dot_PLC_g*PIP2/(Km+PIP2)

449457
type: LocalParameter
units: 443160
value: 97.2222222222222

449456
type: LocalParameter
units: 443196
value: 2.1E-14

450120
type: SpeciesReference
stoichiometry: 1.0
species: 418566

450132
type: SpeciesReference
stoichiometry: 1.0
species: 418926

450107
type: SpeciesReference
stoichiometry: 1.0
species: 422166

420026
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.166666666666667
initial amount: NaN
in compartment: 418386

423045
type: Reaction
kinetic law: 445010
product: 444998
reactant: 444986
notes: Time course of decline of phosph is 20 min. Part of this is the turnoff time of the EGFR itself. Lets assume a tau of 10 min for this dephosph. It may be wildly off.
fast: false
reversible: true

445010
type: KineticLaw
local parameters: 449178
local parameters: 449175
notes: kf*EGFR_slash_SHC_star_-kb*EGFR_slash_SHC

449178
type: LocalParameter
units: 443196
value: 0.0

449175
type: LocalParameter
units: 443196
value: 2.50005E-18

444998
type: SpeciesReference
stoichiometry: 1.0
species: 420106

444986
type: SpeciesReference
stoichiometry: 1.0
species: 420126

425185
type: Reaction
kinetic law: 450460
product: 450448
reactant: 450436
reactant: 450424
notes: See Hanson and Schulman again, for afterburst rates of phosph.
fast: false
reversible: true

450460
type: KineticLaw
local parameters: 449467
local parameters: 449466
notes: k1*CaMKII_slash_CaMKII_minus_thr286*CaMKII_slash_tot_autonomous_CaMKII-k2*CaMKII_slash_tot_autonomous_CaMKII_slash_auton_305_slash_auton_305_cplx

449467
type: LocalParameter
units: 443196
value: 3.6E-14

449466
type: LocalParameter
units: 443280
value: 2.571345E-16

450448
type: SpeciesReference
stoichiometry: 1.0
species: 420506

450436
type: SpeciesReference
stoichiometry: 1.0
species: 422286

450424
type: SpeciesReference
stoichiometry: 1.0
species: 420426

425545
type: Reaction
kinetic law: 451330
product: 451318
reactant: 451306
reactant: 451294
fast: false
reversible: true

451330
type: KineticLaw
local parameters: 449500
local parameters: 449499
notes: k1*PP1_slash_PP1_minus_I1_star_*CaM_po_Ca_pc_n_minus_CaNAB-k2*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_minus_PP1_minus_I_star__slash_dephosph_minus_PP1_minus_I_star__cplx

449500
type: LocalParameter
units: 443196
value: 2.04E-15

449499
type: LocalParameter
units: 443280
value: 5.13E-16

451318
type: SpeciesReference
stoichiometry: 1.0
species: 419606

451306
type: SpeciesReference
stoichiometry: 1.0
species: 422305

451294
type: SpeciesReference
stoichiometry: 1.0
species: 420866

422426
type: Reaction
kinetic law: 443559
product: 443547
reactant: 443535
reactant: 443522
notes: kf raised 10 X based on Shinomura et al PNAS 88 5149-5153 1991 closer analysis of Shinomura et al: kf now 1e-8 (was 1.66e-8). Further tweak. To get sufficient AA synergy, increase kf to 1.5e-8 26 June 1996: Corrected DAG levels: reduce kf by 15x from 1.5e-8 to 1e-9
fast: false
reversible: true

443559
type: KineticLaw
local parameters: 449050
local parameters: 449047
notes: kf*PKC_slash_PKC_minus_cytosolic*DAG-kb*PKC_slash_PKC_minus_DAG

449050
type: LocalParameter
units: 443196
value: 1.5E-16

449047
type: LocalParameter
units: 443280
value: 9.000045E-19

443547
type: SpeciesReference
stoichiometry: 1.0
species: 418506

418506
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.161E-16
initial amount: NaN
in compartment: 418386

443535
type: SpeciesReference
stoichiometry: 1.0
species: 418566

443522
type: SpeciesReference
stoichiometry: 1.0
species: 418526

426145
type: Reaction
kinetic law: 452786
product: 452774
product: 452762
reactant: 452750
fast: false
reversible: false

452786
type: KineticLaw
local parameters: 449561
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_raf_slash_PKC_minus_act_minus_raf_cplx

449561
type: LocalParameter
units: 443196
value: 6.0E-15

452774
type: SpeciesReference
stoichiometry: 1.0
species: 422325

452762
type: SpeciesReference
stoichiometry: 1.0
species: 419266

452750
type: SpeciesReference
stoichiometry: 1.0
species: 421826

425525
type: Reaction
kinetic law: 451282
product: 451270
product: 451258
reactant: 451246
fast: false
reversible: false

451282
type: KineticLaw
local parameters: 449498
notes: k3*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_inhib1_slash_dephosph_inhib1_cplx

449498
type: LocalParameter
units: 443196
value: 5.1E-16

451270
type: SpeciesReference
stoichiometry: 1.0
species: 422305

451258
type: SpeciesReference
stoichiometry: 1.0
species: 420826

420826
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.8
initial amount: NaN
in compartment: 418386

451246
type: SpeciesReference
stoichiometry: 1.0
species: 420806

423105
type: Reaction
kinetic law: 445142
product: 445130
reactant: 445118
reactant: 445106
notes: Same rates as Grb2_bind_Sos: Porfiri and McCormick JBC 271:10 pp 5871 1996 show that the binding is not affected by the phosph.
fast: false
reversible: true

445142
type: KineticLaw
local parameters: 449190
local parameters: 449187
notes: kf*Sos_slash_Sos_star_*Sos_slash_Grb2-kb*Sos_slash_Sos_star__dot_Grb2

449190
type: LocalParameter
units: 443196
value: 2.52E-17

449187
type: LocalParameter
units: 443280
value: 3.75003E-17

445130
type: SpeciesReference
stoichiometry: 1.0
species: 420166

445118
type: SpeciesReference
stoichiometry: 1.0
species: 420186

445106
type: SpeciesReference
stoichiometry: 1.0
species: 420226

423405
type: Reaction
kinetic law: 445817
product: 445805
product: 445793
reactant: 445781
notes: Let us assume that the equil in this case is very far over to the right. This is probably safe.
fast: false
reversible: true

445817
type: KineticLaw
local parameters: 449250
local parameters: 449247
notes: kf*PP1_slash_PP1_minus_I1-kb*PP1_minus_active*PP1_slash_I1

449250
type: LocalParameter
units: 443280
value: 0.0

449247
type: LocalParameter
units: 443196
value: 1.5E-15

445805
type: SpeciesReference
stoichiometry: 1.0
species: 420826

445793
type: SpeciesReference
stoichiometry: 1.0
species: 420546

445781
type: SpeciesReference
stoichiometry: 1.0
species: 420886

424625
type: Reaction
kinetic law: 448690
product: 448678
reactant: 448665
reactant: 448653
notes: Ueki et al JBC 269(22) pp 15756-15761 1994 show hyperphosphorylation of craf, so this is there to dephosphorylate it. Identity of phosphatase is not known to me, but it may be PP2A like the rest, so I have made it so.
fast: false
reversible: true

449418
type: LocalParameter
units: 443196
value: 3.6E-14

449417
type: LocalParameter
units: 443280
value: 2.87415E-15

448678
type: SpeciesReference
stoichiometry: 1.0
species: 419586

419586
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

448665
type: SpeciesReference
stoichiometry: 1.0
species: 419506

448653
type: SpeciesReference
stoichiometry: 1.0
species: 419326

422186
type: Species
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

426025
type: Reaction
kinetic law: 452497
product: 452484
product: 452472
reactant: 452460
fast: false
reversible: false

452497
type: KineticLaw
local parameters: 449552
notes: k3*MKP3_slash_MKP_minus_3_slash_MKP3_minus_thr_minus_deph_slash_MKP3_minus_thr_minus_deph_cplx

449552
type: LocalParameter
units: 443196
value: 6.0E-15

452484
type: SpeciesReference
stoichiometry: 1.0
species: 421726

452472
type: SpeciesReference
stoichiometry: 1.0
species: 419346

452460
type: SpeciesReference
stoichiometry: 1.0
species: 421746

422625
type: Reaction
kinetic law: 444042
product: 444030
reactant: 444018
reactant: 444006
notes: Affinity for Gq is > 20 nM (Smrcka et al Science251 804-807 1991) so [Gq].kf = kb so 40nM * 6e5 = kb/kf = 24e3 so kf = 4.2e-5, kb =1
fast: false
reversible: true

444042
type: KineticLaw
local parameters: 449094
local parameters: 449091
notes: kf*G_star_GTP*PLCbeta_slash_PLC_minus_Ca-kb*PLCbeta_slash_PLC_minus_Ca_minus_Gq

449094
type: LocalParameter
units: 443196
value: 1.5E-15

449091
type: LocalParameter
units: 443280
value: 3.78E-14

444030
type: SpeciesReference
stoichiometry: 1.0
species: 419006

444018
type: SpeciesReference
stoichiometry: 1.0
species: 418966

444006
type: SpeciesReference
stoichiometry: 1.0
species: 419086

426245
type: Reaction
kinetic law: 453027
product: 453015
reactant: 453003
reactant: 452991
notes: Rates from Huang et al ABB 305:2 570-580 1993
fast: false
reversible: true

453027
type: KineticLaw
local parameters: 449572
local parameters: 449571
notes: k1*CaM_slash_neurogranin*PKC_minus_active-k2*PKC_minus_active_slash_PKC_minus_phosph_minus_neurogranin_slash_PKC_minus_phosph_minus_neurogranin_cplx

449572
type: LocalParameter
units: 443196
value: 3.51E-15

449571
type: LocalParameter
units: 443280
value: 1.529955E-16

453015
type: SpeciesReference
stoichiometry: 1.0
species: 421886

453003
type: SpeciesReference
stoichiometry: 1.0
species: 422325

452991
type: SpeciesReference
stoichiometry: 1.0
species: 420726

425585
type: Reaction
kinetic law: 451426
product: 451414
reactant: 451402
reactant: 451390
notes: PP2A does most of the dephosph of I1 at basal Ca levels. See the review by Cohen in Ann Rev Biochem 1989. For now, lets halve Km. k1 was 3.3e-6, now 6.6e-6
fast: false
reversible: true

451426
type: KineticLaw
local parameters: 449503
local parameters: 449502
notes: k1*PP1_slash_I1_star_*PP2A-k2*PP2A_slash_PP2A_minus_dephosph_minus_I1_slash_PP2A_minus_dephosph_minus_I1_cplx

449503
type: LocalParameter
units: 443196
value: 3.75E-14

449502
type: LocalParameter
units: 443280
value: 5.94E-15

451414
type: SpeciesReference
stoichiometry: 1.0
species: 420926

420926
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

451402
type: SpeciesReference
stoichiometry: 1.0
species: 420906

451390
type: SpeciesReference
stoichiometry: 1.0
species: 420846

424025
type: Reaction
kinetic law: 447217
product: 447205
reactant: 447193
reactant: 447181
notes: 10 x raise oct 22 12 x and rescale for k2 = 4 * k3 convention oct 24 Increase further to get the match to expt, which was spoilt due to large accumulation of PLA2 in the enzyme complexed forms. Lets raise k3, leaving the others at k1 = 1.5e-5 and k2 = 144 since they are large already.
fast: false
reversible: true

447217
type: KineticLaw
local parameters: 449364
local parameters: 449363
notes: k1*PLA2_slash_APC*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star_-k2*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx

449364
type: LocalParameter
units: 443196
value: 2.16E-13

449363
type: LocalParameter
units: 443280
value: 1.35E-14

447205
type: SpeciesReference
stoichiometry: 1.0
species: 418726

447193
type: SpeciesReference
stoichiometry: 1.0
species: 418706

447181
type: SpeciesReference
stoichiometry: 1.0
species: 422066

421986
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

423265
type: Reaction
kinetic law: 445492
product: 445480
reactant: 445468
notes: This reaction represents one of the big unknowns in CaMK-II biochemistry: what maintains the basal level of phosphorylation on thr 286 ? See Hanson and Schulman Ann Rev Biochem 1992 61:559-601, specially pg 580, for review. I have not been able to find any compelling mechanism in the literature, but fortunately the level of basal activity is well documented.
fast: false
reversible: true

445492
type: KineticLaw
local parameters: 449222
local parameters: 449219
notes: kf*CaMKII_slash_CaMKII-kb*CaMKII_slash_CaMKII_minus_thr286

449222
type: LocalParameter
units: 443196
value: 0.0

449219
type: LocalParameter
units: 443196
value: 4.5E-18

445480
type: SpeciesReference
stoichiometry: 1.0
species: 420426

445468
type: SpeciesReference
stoichiometry: 1.0
species: 420346

426365
type: Reaction
kinetic law: 453327
product: 453315
reactant: 453303
reactant: 453291
fast: false
reversible: true

453327
type: KineticLaw
local parameters: 449581
local parameters: 449580
notes: k1*PKM_slash_AA_pool*PKM_slash_PKM_synthesis-k2*PKM_slash_PKM_synthesis_slash_kenz_slash_kenz_cplx

449581
type: LocalParameter
units: 443196
value: 3.0E-16

449580
type: LocalParameter
units: 443280
value: 3.75003E-17

453315
type: SpeciesReference
stoichiometry: 1.0
species: 421986

453303
type: SpeciesReference
stoichiometry: 1.0
species: 421966

453291
type: SpeciesReference
stoichiometry: 1.0
species: 422246

424985
type: Reaction
kinetic law: 449951
product: 449939
reactant: 449927
reactant: 449915
notes: Hsu et al JBC 266:1 603-608 1991 Km = 385 +- 100 uM, Vm = 5.1 +-1 pmol/min/ug for PLC-771. Other sites have similar range, but are not stim as much by EGF. k1 = 2.8e-2/385/6e5 = 1.2e-10. Phenomenally slow. But Sherrill and Kyte say turnover # for angiotensin II is 5/min for cell extt, and 2/min for placental. Also see Okada et al for Shc rates which are much faster.
fast: false
reversible: true

449951
type: KineticLaw
local parameters: 449451
local parameters: 449450
notes: k1*PLC_g_slash_Ca_dot_PLC_g*EGFR_slash_L_dot_EGFR-k2*EGFR_slash_L_dot_EGFR_slash_phosph_PLC_g_slash_phosph_PLC_g_cplx

449451
type: LocalParameter
units: 443196
value: 1.2E-15

449450
type: LocalParameter
units: 443280
value: 4.499955E-15

449939
type: SpeciesReference
stoichiometry: 1.0
species: 420066

449927
type: SpeciesReference
stoichiometry: 1.0
species: 420046

449915
type: SpeciesReference
stoichiometry: 1.0
species: 420306

424645
type: Reaction
kinetic law: 448738
product: 448726
product: 448714
reactant: 448702
fast: false
reversible: false

449419
type: LocalParameter
units: 443196
value: 9.0E-15

448726
type: SpeciesReference
stoichiometry: 1.0
species: 419506

448714
type: SpeciesReference
stoichiometry: 1.0
species: 419266

448702
type: SpeciesReference
stoichiometry: 1.0
species: 419586

426225
type: Reaction
kinetic law: 452979
product: 452967
product: 452955
reactant: 452943
fast: false
reversible: false

452979
type: KineticLaw
local parameters: 449570
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_GEF_slash_PKC_minus_act_minus_GEF_cplx

449570
type: LocalParameter
units: 443196
value: 6.0E-15

452967
type: SpeciesReference
stoichiometry: 1.0
species: 422325

452955
type: SpeciesReference
stoichiometry: 1.0
species: 419686

452943
type: SpeciesReference
stoichiometry: 1.0
species: 421866

423785
type: Reaction
kinetic law: 446709
product: 446697
reactant: 446685
reactant: 446673
notes: For olf epi PDE1, affinity is 7 nM. Assume same for brain. Reaction should be pretty fast. Assume kb = 5/sec. Then kf = 5 / (0.007 * 6e5) = 1.2e-3
fast: false
reversible: true

446709
type: KineticLaw
local parameters: 449326
local parameters: 449323
notes: kf*AC_slash_PDE1*CaM_minus_Ca4-kb*AC_slash_CaM_dot_PDE1

449326
type: LocalParameter
units: 443196
value: 7.5E-15

449323
type: LocalParameter
units: 443280
value: 1.08E-12

446697
type: SpeciesReference
stoichiometry: 1.0
species: 421586

446685
type: SpeciesReference
stoichiometry: 1.0
species: 419966

446673
type: SpeciesReference
stoichiometry: 1.0
species: 421546

425825
type: Reaction
kinetic law: 452013
product: 452001
product: 451989
reactant: 451977
fast: false
reversible: false

452013
type: KineticLaw
local parameters: 449534
notes: k3*AC_slash_cAMP_minus_PDE_slash_PDE_slash_PDE_cplx

449534
type: LocalParameter
units: 443196
value: 1.5E-14

452001
type: SpeciesReference
stoichiometry: 1.0
species: 421466

451989
type: SpeciesReference
stoichiometry: 1.0
species: 421426

451977
type: SpeciesReference
stoichiometry: 1.0
species: 421486

423505
type: Reaction
kinetic law: 446057
product: 446045
reactant: 446033
reactant: 446021
fast: false
reversible: true

446057
type: KineticLaw
local parameters: 449270
local parameters: 449267
notes: kf*CaM_minus_Ca4*CaNAB_minus_Ca4-kb*PP2B_slash_CaMCa4_minus_CaNAB

449270
type: LocalParameter
units: 443196
value: 1.5E-15

449267
type: LocalParameter
units: 443280
value: 9.000045E-13

446045
type: SpeciesReference
stoichiometry: 1.0
species: 421086

446033
type: SpeciesReference
stoichiometry: 1.0
species: 420966

446021
type: SpeciesReference
stoichiometry: 1.0
species: 419966

423365
type: Reaction
kinetic law: 445720
product: 445708
reactant: 445696
notes: This is put in to keep the basal levels of neurogranin* experimentally reasonable. From various papers, specially Ramakers et al JBC 270:23 1995 13892-13898, it looks like the basal level of phosph is between 20 and 40%. I est around 25 % The kf of 0.005 gives around this level at basal PKC activity levels of 0.1 uM active PKC.
fast: false
reversible: true

445720
type: KineticLaw
local parameters: 449242
local parameters: 449239
notes: kf*CaM_slash_neurogranin_star_-kb*CaM_slash_neurogranin

449242
type: LocalParameter
units: 443196
value: 0.0

449239
type: LocalParameter
units: 443196
value: 7.5E-18

445708
type: SpeciesReference
stoichiometry: 1.0
species: 420726

445696
type: SpeciesReference
stoichiometry: 1.0
species: 420706

422705
type: Reaction
kinetic law: 444235
product: 444223
reactant: 444211
reactant: 444199
notes: kf = kf from text = 1e7 / M / sec = 10 /uM/sec = 10 / 6e5 / # / sec = 1.67e-5 kb = kr from text = 60 / sec Note that we continue to use uM here since [phenylephrine] is also in uM. From Martin et al FEBS Lett 316:2 191-196 1993 we have Kd = 600 nM Assuming kb = 10/sec, we get kf = 10/(0.6 uM * 6e5) = 2.8e-5 1/sec/#
fast: false
reversible: true

444235
type: KineticLaw
local parameters: 449110
local parameters: 449107
notes: kf*Gq_slash_mGluR*Glu-kb*Gq_slash_Rec_minus_Glu

449110
type: LocalParameter
units: 443196
value: 1.5E-14

449107
type: LocalParameter
units: 443280
value: 2.520045E-14

444223
type: SpeciesReference
stoichiometry: 1.0
species: 419166

444211
type: SpeciesReference
stoichiometry: 1.0
species: 422106

444199
type: SpeciesReference
stoichiometry: 1.0
species: 419146

425205
type: Reaction
kinetic law: 450508
product: 450496
product: 450484
reactant: 450472
fast: false
reversible: false

450508
type: KineticLaw
local parameters: 449468
notes: k3*CaMKII_slash_tot_autonomous_CaMKII_slash_auton_305_slash_auton_305_cplx

449468
type: LocalParameter
units: 443196
value: 9.0E-15

450496
type: SpeciesReference
stoichiometry: 1.0
species: 422286

450484
type: SpeciesReference
stoichiometry: 1.0
species: 420406

450472
type: SpeciesReference
stoichiometry: 1.0
species: 420506

424865
type: Reaction
kinetic law: 449659
product: 449647
reactant: 449635
reactant: 449623
notes: #s from Bramson et al CRC crit rev Biochem 15:2 93-124. They have a huge list of peptide substrates and I have chosen high-ish rates. These consts give too much PKA activity, so lower Vmax 1/3. Now, k1 = 3e-5, k2 = 36, k3 = 9 (still pretty fast). Also lower Km 1/3 so k1 = 1e-5 Cohen et al FEBS Lett 76:182-86 1977 say rate =30% PKA act on phosphokinase beta.
fast: false
reversible: true

449659
type: KineticLaw
local parameters: 449439
local parameters: 449438
notes: k1*PP1_slash_I1*PKA_minus_active-k2*PKA_minus_active_slash_PKA_minus_phosph_minus_I1_slash_PKA_minus_phosph_minus_I1_cplx

449439
type: LocalParameter
units: 443196
value: 5.4E-14

449438
type: LocalParameter
units: 443280
value: 9.000045E-15

449647
type: SpeciesReference
stoichiometry: 1.0
species: 419926

419926
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

449635
type: SpeciesReference
stoichiometry: 1.0
species: 419886

449623
type: SpeciesReference
stoichiometry: 1.0
species: 420826

424465
type: Reaction
kinetic law: 448304
product: 448292
reactant: 448280
reactant: 448268
notes: Same kinetics as other c-raf activated forms. See Force et al PNAS 91 1270-1274 1994. k1 = 1.1e-6, k2 = .42, k3 = 1.05 raise k1 to 5.5e-6
fast: false
reversible: true

448304
type: KineticLaw
local parameters: 449403
local parameters: 449402
notes: k1*MAPK_slash_MAPKK_minus_ser*MAPK_slash_Raf_star__minus_GTP_minus_Ras-k2*MAPK_slash_Raf_star__minus_GTP_minus_Ras_slash_Raf_star__minus_GTP_minus_Ras_dot_2_slash_Raf_star__minus_GTP_minus_Ras_dot_2_cplx

449403
type: LocalParameter
units: 443196
value: 1.8E-15

449402
type: LocalParameter
units: 443280
value: 1.41426E-14

448292
type: SpeciesReference
stoichiometry: 1.0
species: 419486

448280
type: SpeciesReference
stoichiometry: 1.0
species: 419446

448268
type: SpeciesReference
stoichiometry: 1.0
species: 419426

425685
type: Reaction
kinetic law: 451676
product: 451663
product: 451651
reactant: 451639
fast: false
reversible: false

451676
type: KineticLaw
local parameters: 449513
notes: k3*CaNAB_minus_Ca4_slash_dephosph_inhib1_noCaM_slash_dephosph_inhib1_noCaM_cplx

449513
type: LocalParameter
units: 443196
value: 5.1E-17

451663
type: SpeciesReference
stoichiometry: 1.0
species: 420966

451651
type: SpeciesReference
stoichiometry: 1.0
species: 420826

451639
type: SpeciesReference
stoichiometry: 1.0
species: 420986

423665
type: Reaction
kinetic law: 446443
product: 446431
reactant: 446419
reactant: 446407
notes: Half-max at 20 nM CaM (Tang et al JBC 266:13 8595-8603 1991 kb/kf = 20 nM = 12000 #/cell so kf = kb/12000 = kb * 8.333e-5
fast: false
reversible: true

446443
type: KineticLaw
local parameters: 449302
local parameters: 449299
notes: kf*CaM_minus_Ca4*AC_slash_AC1-kb*AC_slash_AC1_minus_CaM

449302
type: LocalParameter
units: 443196
value: 1.5E-15

449299
type: LocalParameter
units: 443280
value: 7.499925E-14

446431
type: SpeciesReference
stoichiometry: 1.0
species: 421306

446419
type: SpeciesReference
stoichiometry: 1.0
species: 421326

446407
type: SpeciesReference
stoichiometry: 1.0
species: 419966

423585
type: Reaction
kinetic law: 446250
product: 446238
reactant: 446226
reactant: 446214
fast: false
reversible: true

446250
type: KineticLaw
local parameters: 449286
local parameters: 449283
notes: kf*cAMP*PKA_slash_R2C2_minus_cAMP3-kb*PKA_slash_R2C2_minus_cAMP4

449286
type: LocalParameter
units: 443196
value: 4.875E-14

449283
type: LocalParameter
units: 443280
value: 1.1249955E-13

446238
type: SpeciesReference
stoichiometry: 1.0
species: 421186

446226
type: SpeciesReference
stoichiometry: 1.0
species: 421166

446214
type: SpeciesReference
stoichiometry: 1.0
species: 421286

425505
type: Reaction
kinetic law: 451234
product: 451222
reactant: 451210
reactant: 451198
fast: false
reversible: true

451234
type: KineticLaw
local parameters: 449497
local parameters: 449496
notes: k1*PP1_slash_I1_star_*CaM_po_Ca_pc_n_minus_CaNAB-k2*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_inhib1_slash_dephosph_inhib1_cplx

449497
type: LocalParameter
units: 443196
value: 2.04E-15

449496
type: LocalParameter
units: 443280
value: 5.13E-16

451222
type: SpeciesReference
stoichiometry: 1.0
species: 420806

451210
type: SpeciesReference
stoichiometry: 1.0
species: 422305

451198
type: SpeciesReference
stoichiometry: 1.0
species: 420846

422525
type: Reaction
kinetic law: 443790
product: 443778
reactant: 443766
notes: I need to check if the AA degradation pathway really leads back to APC. Anyway, it is a convenient buffered pool to dump it back into. For the purposes of the full model we use a rate of degradation of 0.2/sec Raised decay to 0.4 : see PLA35.g notes for Feb17
fast: false
reversible: true

443790
type: KineticLaw
local parameters: 449070
local parameters: 449067
notes: kf*AA-kb*PLA2_slash_APC

449070
type: LocalParameter
units: 443196
value: 0.0

449067
type: LocalParameter
units: 443196
value: 6.0E-16

443778
type: SpeciesReference
stoichiometry: 1.0
species: 422066

443766
type: SpeciesReference
stoichiometry: 1.0
species: 418586

425785
type: Reaction
kinetic law: 451917
modifier: 451905
product: 451893
reactant: 451881
fast: false
reversible: false

451917
type: KineticLaw
local parameters: 449529
local parameters: 449526
notes: kcat*AC_slash_AC2_star__minus_Gs*AC_slash_ATP/(Km+AC_slash_ATP)

449529
type: LocalParameter
units: 443160
value: 60.0

449526
type: LocalParameter
units: 443196
value: 8.1E-14

451893
type: SpeciesReference
stoichiometry: 1.0
species: 421286

451881
type: SpeciesReference
stoichiometry: 1.0
species: 422205

424665
type: Reaction
kinetic law: 448786
product: 448774
reactant: 448762
reactant: 448750
notes: Kinetics based on the activation of Gq by the receptor complex in the Gq model (in turn based on the Mahama and Linderman model) k1 = 2e-5, k2 = 1e-10, k3 = 10 (I do not know why they even bother with k2). Lets put k1 at 2e-6 to get a reasonable equilibrium More specific values from, eg.g: Orita et al JBC 268(34) 25542-25546 from rasGRF and smgGDS: k1=3.3e-7; k2 = 0.08, k3 = 0.02
fast: false
reversible: true

448786
type: KineticLaw
local parameters: 449421
local parameters: 449420
notes: k1*Ras_slash_GDP_minus_Ras*Ras_slash_GEF_minus_Gprot_minus_bg-k2*Ras_slash_GEF_minus_Gprot_minus_bg_slash_GEF_minus_bg_act_minus_ras_slash_GEF_minus_bg_act_minus_ras_cplx

449421
type: LocalParameter
units: 443196
value: 1.2E-16

449420
type: LocalParameter
units: 443280
value: 2.97E-16

448774
type: SpeciesReference
stoichiometry: 1.0
species: 419646

448762
type: SpeciesReference
stoichiometry: 1.0
species: 419626

448750
type: SpeciesReference
stoichiometry: 1.0
species: 419746

422645
type: Reaction
kinetic law: 444090
product: 444078
product: 444066
reactant: 444054
notes: This process is assumed to be directly caused by the inactivation of the G*GTP to G*GDP. Hence, kf = .013 /sec = 0.8/min, same as the rate for Inact-G. kb = 0 since this is irreversible. We may be interested in studying the role of PLC as a GAP. If so, the kf would be faster here than in Inact-G
fast: false
reversible: true

444090
type: KineticLaw
local parameters: 449098
local parameters: 449095
notes: kf*PLCbeta_slash_PLC_minus_Ca_minus_Gq-kb*G_star_GDP*PLCbeta_slash_PLC_minus_Ca

449098
type: LocalParameter
units: 443280
value: 0.0

449095
type: LocalParameter
units: 443196
value: 1.995E-17

444078
type: SpeciesReference
stoichiometry: 1.0
species: 418966

444066
type: SpeciesReference
stoichiometry: 1.0
species: 419106

444054
type: SpeciesReference
stoichiometry: 1.0
species: 419006

425605
type: Reaction
kinetic law: 451474
product: 451462
product: 451450
reactant: 451438
fast: false
reversible: false

451474
type: KineticLaw
local parameters: 449504
notes: k3*PP2A_slash_PP2A_minus_dephosph_minus_I1_slash_PP2A_minus_dephosph_minus_I1_cplx

449504
type: LocalParameter
units: 443196
value: 9.0E-15

451462
type: SpeciesReference
stoichiometry: 1.0
species: 420906

451450
type: SpeciesReference
stoichiometry: 1.0
species: 420826

451438
type: SpeciesReference
stoichiometry: 1.0
species: 420926

426385
type: Reaction
kinetic law: 453375
product: 453363
product: 453351
reactant: 453339
fast: false
reversible: false

453375
type: KineticLaw
local parameters: 449582
notes: k3*PKM_slash_PKM_synthesis_slash_kenz_slash_kenz_cplx

449582
type: LocalParameter
units: 443196
value: 7.5E-17

453363
type: SpeciesReference
stoichiometry: 1.0
species: 421966

453351
type: SpeciesReference
stoichiometry: 1.0
species: 418546

453339
type: SpeciesReference
stoichiometry: 1.0
species: 421986

424105
type: Reaction
kinetic law: 447412
product: 447400
reactant: 447388
reactant: 447376
notes: This form should be 3 to 6 times as fast as the Ca-only form. I have scaled by 4x which seems to give a 5x rise. 10x raise Oct 22 12 x oct 24, changed k2 = 4 * k3
fast: false
reversible: true

447412
type: KineticLaw
local parameters: 449370
local parameters: 449369
notes: k1*PLA2_slash_APC*PLA2_slash_PLA2_star__minus_Ca-k2*PLA2_slash_PLA2_star__minus_Ca_slash_kenz_slash_kenz_cplx

449370
type: LocalParameter
units: 443196
value: 7.2E-13

449369
type: LocalParameter
units: 443280
value: 4.499955E-14

447400
type: SpeciesReference
stoichiometry: 1.0
species: 418806

447388
type: SpeciesReference
stoichiometry: 1.0
species: 418786

447376
type: SpeciesReference
stoichiometry: 1.0
species: 422066

423605
type: Reaction
kinetic law: 446298
product: 446286
product: 446274
reactant: 446262
notes: This has to be fast, as the activation of PKA by cAMP is also fast. kf was 10
fast: false
reversible: true

446298
type: KineticLaw
local parameters: 449290
local parameters: 449287
notes: kf*PKA_slash_R2C2_minus_cAMP4-kb*PKA_minus_active*PKA_slash_R2C_minus_cAMP4

449290
type: LocalParameter
units: 443280
value: 2.7E-14

449287
type: LocalParameter
units: 443196
value: 9.0E-14

446286
type: SpeciesReference
stoichiometry: 1.0
species: 421206

446274
type: SpeciesReference
stoichiometry: 1.0
species: 419886

446262
type: SpeciesReference
stoichiometry: 1.0
species: 421186

424285
type: Reaction
kinetic law: 447859
product: 447846
product: 447834
product: 447822
reactant: 447810
fast: false
reversible: false

447859
type: KineticLaw
local parameters: 449386
notes: k3*PLCbeta_slash_PLC_minus_Ca_slash_PLC_minus_Ca_slash_PLC_minus_Ca_cplx

449386
type: LocalParameter
units: 443196
value: 1.5E-14

447846
type: SpeciesReference
stoichiometry: 1.0
species: 418966

447834
type: SpeciesReference
stoichiometry: 1.0
species: 418926

447822
type: SpeciesReference
stoichiometry: 1.0
species: 418566

447810
type: SpeciesReference
stoichiometry: 1.0
species: 418986

425005
type: Reaction
kinetic law: 449999
product: 449987
product: 449975
reactant: 449963
fast: false
reversible: false

449999
type: KineticLaw
local parameters: 449452
notes: k3*EGFR_slash_L_dot_EGFR_slash_phosph_PLC_g_slash_phosph_PLC_g_cplx

449452
type: LocalParameter
units: 443196
value: 3.0E-16

449987
type: SpeciesReference
stoichiometry: 1.0
species: 420046

449975
type: SpeciesReference
stoichiometry: 1.0
species: 420326

449963
type: SpeciesReference
stoichiometry: 1.0
species: 420066

422565
type: Reaction
kinetic law: 443874
product: 443862
reactant: 443850
fast: false
reversible: true

443874
type: KineticLaw
local parameters: 449078
local parameters: 449075
notes: kf*PLA2_slash_PLA2_star_-kb*PLA2_slash_PLA2_minus_cytosolic

449078
type: LocalParameter
units: 443196
value: 0.0

449075
type: LocalParameter
units: 443196
value: 2.55E-16

443862
type: SpeciesReference
stoichiometry: 1.0
species: 418606

443850
type: SpeciesReference
stoichiometry: 1.0
species: 418826

422865
type: Reaction
kinetic law: 444638
product: 444626
reactant: 444614
reactant: 444601
notes: The rate consts give a total binding affinity of only
fast: false
reversible: true

444638
type: KineticLaw
local parameters: 449142
local parameters: 449139
notes: kf*Gq_slash_Rec_minus_Gq*Gq_slash_mGluRAntag-kb*Gq_slash_Blocked_minus_rec_minus_Gq

449142
type: LocalParameter
units: 443196
value: 1.5E-17

449139
type: LocalParameter
units: 443280
value: 9.000045E-14

444626
type: SpeciesReference
stoichiometry: 1.0
species: 419226

419226
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386

444614
type: SpeciesReference
stoichiometry: 1.0
species: 422185

444601
type: SpeciesReference
stoichiometry: 1.0
species: 419186

425625
type: Reaction
kinetic law: 451523
product: 451510
reactant: 451498
reactant: 451486
notes: k1 changed from 3.3e-6 to 6.6e-6
fast: false
reversible: true

451523
type: KineticLaw
local parameters: 449506
local parameters: 449505
notes: k1*PP1_slash_PP1_minus_I1_star_*PP2A-k2*PP2A_slash_PP2A_minus_dephosph_minus_PP1_minus_I_star__slash_PP2A_minus_dephosph_minus_PP1_minus_I_star__cplx

449506
type: LocalParameter
units: 443196
value: 3.75E-14

449505
type: LocalParameter
units: 443280
value: 5.94E-15

451510
type: SpeciesReference
stoichiometry: 1.0
species: 420946

451498
type: SpeciesReference
stoichiometry: 1.0
species: 420906

451486
type: SpeciesReference
stoichiometry: 1.0
species: 420866

422845
type: Reaction
kinetic law: 444588
product: 444576
reactant: 444564
reactant: 444552
notes: Lets try out the same kinetics as the Rec-Glu-bind-Gq This is much too forward. We know that the steady-state amount of Rec-Gq should be 40% of the total amount of receptor. This is for a different receptor, still we can try to match the value. kf = 1e-6 and kb = 1 give 0.333:0.8 which is pretty close.
fast: false
reversible: true

444588
type: KineticLaw
local parameters: 449138
local parameters: 449135
notes: kf*Gq_slash_G_minus_GDP*Gq_slash_mGluR-kb*Gq_slash_Rec_minus_Gq

449138
type: LocalParameter
units: 443196
value: 1.5E-15

449135
type: LocalParameter
units: 443280
value: 9.000045E-16

444576
type: SpeciesReference
stoichiometry: 1.0
species: 419186

444564
type: SpeciesReference
stoichiometry: 1.0
species: 419146

444552
type: SpeciesReference
stoichiometry: 1.0
species: 419126

424745
type: Reaction
kinetic law: 448982
product: 448969
reactant: 448957
reactant: 448944
notes: From Eccleston et al JBC 268(36)pp27012-19 get Kd < 2uM, kcat - 10/sec From Martin et al Cell 63 843-849 1990 get Kd ~ 250 nM, kcat = 20/min I will go with the Eccleston figures as there are good error bars (10%). In general the values are reasonably close. k1 = 1.666e-3/sec, k2 = 1000/sec, k3 = 10/sec (note k3 is rate-limiting) 5 Nov 2002: Changed ratio term to 4 from 100. Now we have k1=8.25e-5; k2=40, k3=10. k3 is still rate-limiting.
fast: false
reversible: true

448982
type: KineticLaw
local parameters: 449430
local parameters: 449427
notes: k1*Ras_slash_GTP_minus_Ras*Ras_slash_GAP-k2*Ras_slash_GAP_slash_GAP_minus_inact_minus_ras_slash_GAP_minus_inact_minus_ras_cplx

449430
type: LocalParameter
units: 443196
value: 6.0E-14

449427
type: LocalParameter
units: 443280
value: 7.42284E-14

448969
type: SpeciesReference
stoichiometry: 1.0
species: 419806

448957
type: SpeciesReference
stoichiometry: 1.0
species: 419786

448944
type: SpeciesReference
stoichiometry: 1.0
species: 419726

424345
type: Reaction
kinetic law: 448016
product: 448004
reactant: 447992
reactant: 447980
notes: The actual MAPKK is 2 forms from Seger et al JBC 267:20 14373(1992) Vmax = 150nmol/min/mg From Haystead et al FEBS 306(1):17-22 we get Km=46.6nM for at least one of the phosphs. Putting these together: k3=0.15/sec, scale to get k2=0.6. k1=0.75/46.6nM=2.7e-5
fast: false
reversible: true

448016
type: KineticLaw
local parameters: 449394
local parameters: 449391
notes: k1*MAPK_slash_MAPK*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx

449394
type: LocalParameter
units: 443196
value: 1.8E-15

449391
type: LocalParameter
units: 443280
value: 4.86E-14

448004
type: SpeciesReference
stoichiometry: 1.0
species: 419386

447992
type: SpeciesReference
stoichiometry: 1.0
species: 419366

447980
type: SpeciesReference
stoichiometry: 1.0
species: 419306

423225
type: Reaction
kinetic law: 445408
product: 445395
reactant: 445383
reactant: 445371
notes: This is tricky. There is some cooperativity here arising from interactions between the subunits of the CAMKII holoenzyme. However, the stoichiometry is 1. Kb/Kf = 6e4 #/cell. Rate is fast (see Hanson et al Neuron 12 943-956 1994) so lets say kb = 10. This gives kf = 1.6667e-4 H&S AnnRev Biochem 92 give tau for dissoc as 0.2 sec at low Ca, 0.4 at high. Low Ca = 100 nM = physiol.
fast: false
reversible: true

445408
type: KineticLaw
local parameters: 449214
local parameters: 449211
notes: kf*CaM_minus_Ca4*CaMKII_slash_CaMKII-kb*CaMKII_slash_CaMKII_minus_CaM

449214
type: LocalParameter
units: 443196
value: 7.5E-15

449211
type: LocalParameter
units: 443280
value: 7.499925E-14

445395
type: SpeciesReference
stoichiometry: 1.0
species: 420366

445383
type: SpeciesReference
stoichiometry: 1.0
species: 420346

445371
type: SpeciesReference
stoichiometry: 1.0
species: 419966

424145
type: Reaction
kinetic law: 447509
product: 447497
reactant: 447485
reactant: 447473
notes: Km = 25uM @ 50 uM ATP and 1mg/ml MBP (huge XS of substrate) Vmax = 4124 pmol/min/ml at a conc of 125 pmol/ml of enz, so: k3 = .5/sec (rate limiting) k1 = (k2 + k3)/Km = (.5 + 0)/(25*6e5) = 2e-8 (#/cell)^-1 #s from Sanghera et al JBC 265 pp 52 , 1990. From Nemenoff et al JBC 268(3):1960-1964 - using Sanghera\'s 1e-4 ratio of MAPK to protein, we get k3 = 7/sec from 1000 pmol/min/mg fig 5
fast: false
reversible: true

447509
type: KineticLaw
local parameters: 449376
local parameters: 449373
notes: k1*PLA2_slash_PLA2_minus_cytosolic*MAPK_star_-k2*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx

449376
type: LocalParameter
units: 443196
value: 6.0E-14

449373
type: LocalParameter
units: 443280
value: 2.925045E-15

447497
type: SpeciesReference
stoichiometry: 1.0
species: 418866

447485
type: SpeciesReference
stoichiometry: 1.0
species: 418846

447473
type: SpeciesReference
stoichiometry: 1.0
species: 418606

425845
type: Reaction
kinetic law: 452062
product: 452050
reactant: 452037
reactant: 452025
notes: This form has about twice the activity of the unphosphorylated form. See Sette et al JBC 269:28 18271-18274 1994. We\'ll ignore cGMP effects for now.
fast: false
reversible: true

452062
type: KineticLaw
local parameters: 449536
local parameters: 449535
notes: k1*cAMP*AC_slash_cAMP_minus_PDE_star_-k2*AC_slash_cAMP_minus_PDE_star__slash_PDE_star__slash_PDE_star__cplx

449536
type: LocalParameter
units: 443196
value: 1.2E-13

449535
type: LocalParameter
units: 443280
value: 7.56E-15

452050
type: SpeciesReference
stoichiometry: 1.0
species: 421526

452037
type: SpeciesReference
stoichiometry: 1.0
species: 421506

452025
type: SpeciesReference
stoichiometry: 1.0
species: 421286

423205
type: Reaction
kinetic law: 445359
product: 445347
reactant: 445335
fast: false
reversible: true

445359
type: KineticLaw
local parameters: 449210
local parameters: 449207
notes: kf*PLC_g_slash_Ca_dot_PLC_g_star_-kb*PLC_g_slash_Ca_dot_PLC_g

449210
type: LocalParameter
units: 443196
value: 0.0

449207
type: LocalParameter
units: 443196
value: 7.5E-17

445347
type: SpeciesReference
stoichiometry: 1.0
species: 420306

445335
type: SpeciesReference
stoichiometry: 1.0
species: 420326

425265
type: Reaction
kinetic law: 450654
product: 450642
reactant: 450630
reactant: 450618
notes: The rates are from Stralfors et al Eur J Biochem 149 295-303 giving Vmax = 5.7 umol/min giving k3 = 3.5/sec and k2 = 14. Foulkes et al Eur J Biochem 132 309-313 1983 give Km = 5.1 uM so k1 becomes 5.72e-6 Simonelli 1984 (Grad Thesis, CUNY) showed that other substrates are about 1/10 rate of phosphorylase a, so we reduce k1,k2,k3 by 10 to 5.72e-7, 1.4, 0.35
fast: false
reversible: true

450654
type: KineticLaw
local parameters: 449476
local parameters: 449473
notes: k1*CaMKII_slash_CaMKII_minus_thr286_star__minus_CaM*PP1_minus_active-k2*PP1_minus_active_slash_Deph_minus_thr286_slash_Deph_minus_thr286_cplx

449476
type: LocalParameter
units: 443196
value: 2.1E-15

449473
type: LocalParameter
units: 443280
value: 5.147955E-16

450642
type: SpeciesReference
stoichiometry: 1.0
species: 420566

450630
type: SpeciesReference
stoichiometry: 1.0
species: 420546

450618
type: SpeciesReference
stoichiometry: 1.0
species: 420386

426185
type: Reaction
kinetic law: 452883
product: 452871
product: 452858
reactant: 452846
fast: false
reversible: false

452883
type: KineticLaw
local parameters: 449564
notes: k3*PKC_minus_active_slash_PKC_minus_inact_minus_GAP_slash_PKC_minus_inact_minus_GAP_cplx

449564
type: LocalParameter
units: 443196
value: 6.0E-15

452871
type: SpeciesReference
stoichiometry: 1.0
species: 422325

452858
type: SpeciesReference
stoichiometry: 1.0
species: 419766

452846
type: SpeciesReference
stoichiometry: 1.0
species: 421846

424045
type: Reaction
kinetic law: 447267
product: 447255
product: 447242
reactant: 447230
fast: false
reversible: false

447267
type: KineticLaw
local parameters: 449365
notes: k3*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx

449365
type: LocalParameter
units: 443196
value: 5.4E-14

447255
type: SpeciesReference
stoichiometry: 1.0
species: 418706

447242
type: SpeciesReference
stoichiometry: 1.0
species: 418586

447230
type: SpeciesReference
stoichiometry: 1.0
species: 418726

424565
type: Reaction
kinetic law: 448544
product: 448532
product: 448520
reactant: 448508
fast: false
reversible: false

449413
type: LocalParameter
units: 443196
value: 9.0E-15

448532
type: SpeciesReference
stoichiometry: 1.0
species: 419506

448520
type: SpeciesReference
stoichiometry: 1.0
species: 419426

448508
type: SpeciesReference
stoichiometry: 1.0
species: 419546

424825
type: Reaction
kinetic law: 449393
product: 449357
reactant: 449345
reactant: 449333
notes: This pathway inhibits Ras when cAMP is elevated. See: Hordijk et al JBC 269:5 3534-3538 1994 Burgering et al EMBO J 12:11 4211-4220 1993 The rates are the same as used in PKA-phosph-I1
fast: false
reversible: true

449393
type: KineticLaw
local parameters: 449436
local parameters: 449435
notes: k1*Ras_slash_inact_minus_GEF*PKA_minus_active-k2*PKA_minus_active_slash_PKA_minus_phosph_minus_GEF_slash_PKA_minus_phosph_minus_GEF_cplx

449436
type: LocalParameter
units: 443196
value: 5.4E-14

449435
type: LocalParameter
units: 443280
value: 9.000045E-15

449357
type: SpeciesReference
stoichiometry: 1.0
species: 419906

449345
type: SpeciesReference
stoichiometry: 1.0
species: 419886

449333
type: SpeciesReference
stoichiometry: 1.0
species: 419666

424725
type: Reaction
kinetic law: 448932
product: 448919
product: 448907
reactant: 448895
fast: false
reversible: false

448932
type: KineticLaw
local parameters: 449425
notes: k3*Ras_slash_GEF_star__slash_GEF_star__minus_act_minus_ras_slash_GEF_star__minus_act_minus_ras_cplx

449425
type: LocalParameter
units: 443196
value: 3.0E-17

448919
type: SpeciesReference
stoichiometry: 1.0
species: 419686

448907
type: SpeciesReference
stoichiometry: 1.0
species: 419726

448895
type: SpeciesReference
stoichiometry: 1.0
species: 419706

423905
type: Reaction
kinetic law: 446937
product: 446925
reactant: 446913
notes: Time-course of 2 hours.
fast: false
reversible: true

446937
type: KineticLaw
local parameters: 449350
local parameters: 449347
notes: kf*PKC_slash_PKM_minus_zeta-kb*PKM_slash_degraded_PKM

449350
type: LocalParameter
units: 443196
value: 0.0

449347
type: LocalParameter
units: 443196
value: 7.5E-19

446925
type: SpeciesReference
stoichiometry: 1.0
species: 422265

446913
type: SpeciesReference
stoichiometry: 1.0
species: 418546

426405
type: Reaction
kinetic law: 453424
product: 453412
reactant: 453399
reactant: 453387
fast: false
reversible: true

453424
type: KineticLaw
local parameters: 449587
local parameters: 449584
notes: k1*PKM_slash_PKM_activator*PKM_slash_Ca_dot_detector_complex-k2*PKM_slash_Ca_dot_detector_complex_slash_kenz_slash_kenz_cplx

449587
type: LocalParameter
units: 443196
value: 1.2E-15

449584
type: LocalParameter
units: 443280
value: 2.99997E-16

453412
type: SpeciesReference
stoichiometry: 1.0
species: 422026

453399
type: SpeciesReference
stoichiometry: 1.0
species: 422006

453387
type: SpeciesReference
stoichiometry: 1.0
species: 422046

425645
type: Reaction
kinetic law: 451576
product: 451562
product: 451549
reactant: 451536
fast: false
reversible: false

451576
type: KineticLaw
local parameters: 449507
notes: k3*PP2A_slash_PP2A_minus_dephosph_minus_PP1_minus_I_star__slash_PP2A_minus_dephosph_minus_PP1_minus_I_star__cplx

449507
type: LocalParameter
units: 443196
value: 9.0E-15

451562
type: SpeciesReference
stoichiometry: 1.0
species: 420906

451549
type: SpeciesReference
stoichiometry: 1.0
species: 420886

451536
type: SpeciesReference
stoichiometry: 1.0
species: 420946

423425
type: Reaction
kinetic law: 445865
product: 445853
reactant: 445841
reactant: 445829
notes: This process is probably much more complicated and involves CaM. However, as I can\'t find detailed info I am bundling this into a single step. Based on Steemer and Klee pg 6863, the Kact is 0.5 uM. kf/kb = 1/(0.5 * 6e5)^2 = 1.11e-11
fast: false
reversible: true

445865
type: KineticLaw
local parameters: 449254
local parameters: 449251
notes: kf*Ca^2*PP2B_slash_CaNAB_minus_Ca2-kb*CaNAB_minus_Ca4

449254
type: LocalParameter
units: 443196
value: 1.5E-15

449251
type: LocalParameter
units: 443232
value: 5.399946E-15

445853
type: SpeciesReference
stoichiometry: 1.0
species: 420966

445841
type: SpeciesReference
stoichiometry: 1.0
species: 421026

445829
type: SpeciesReference
stoichiometry: 2.0
species: 421646

423025
type: Reaction
kinetic law: 444974
product: 444962
reactant: 444950
reactant: 444938
notes: Affinity of EGFR for EGF is complex: depends on [EGFR]. We\'ll assume fixed [EGFR] and use exptal affinity ~20 nM (see Sherrill and Kyte Biochem 1996 35 5705-5718, Berkers et al JBC 266:2 922-927 1991, Sorokin et al JBC 269:13 9752-9759 1994). Tau =~2 min (Davis et al JBC 263:11 5373-5379 1988) or Berkers Kass = 6.2e5/M/sec, Kdiss=3.5e-4/sec. Sherrill and Kyte have Hill Coeff=1.7
fast: false
reversible: true

444974
type: KineticLaw
local parameters: 449174
local parameters: 449171
notes: kf*EGFR_slash_EGFR*EGFR_slash_EGF-kb*EGFR_slash_L_dot_EGFR

449174
type: LocalParameter
units: 443196
value: 3.75E-16

449171
type: LocalParameter
units: 443280
value: 6.300045E-15

444962
type: SpeciesReference
stoichiometry: 1.0
species: 420046

444950
type: SpeciesReference
stoichiometry: 1.0
species: 422186

444938
type: SpeciesReference
stoichiometry: 1.0
species: 420026

423625
type: Reaction
kinetic law: 446347
product: 446335
product: 446322
reactant: 446310
fast: false
reversible: true

446347
type: KineticLaw
local parameters: 449294
local parameters: 449291
notes: kf*PKA_slash_R2C_minus_cAMP4-kb*PKA_minus_active*PKA_slash_R2_minus_cAMP4

449294
type: LocalParameter
units: 443280
value: 2.7E-14

449291
type: LocalParameter
units: 443196
value: 9.0E-14

446335
type: SpeciesReference
stoichiometry: 1.0
species: 421226

446322
type: SpeciesReference
stoichiometry: 1.0
species: 419886

446310
type: SpeciesReference
stoichiometry: 1.0
species: 421206

425125
type: Reaction
kinetic law: 450315
product: 450303
product: 450291
reactant: 450279
fast: false
reversible: false

450315
type: KineticLaw
local parameters: 449462
notes: k3*CaMKII_slash_tot_CaM_CaMKII_slash_CaM_act_305_slash_CaM_act_305_cplx

449462
type: LocalParameter
units: 443196
value: 9.0E-15

450303
type: SpeciesReference
stoichiometry: 1.0
species: 422285

450291
type: SpeciesReference
stoichiometry: 1.0
species: 420406

450279
type: SpeciesReference
stoichiometry: 1.0
species: 420466

424885
type: Reaction
kinetic law: 449708
product: 449696
product: 449683
reactant: 449671
fast: false
reversible: false

449708
type: KineticLaw
local parameters: 449440
notes: k3*PKA_minus_active_slash_PKA_minus_phosph_minus_I1_slash_PKA_minus_phosph_minus_I1_cplx

449440
type: LocalParameter
units: 443196
value: 1.35E-14

449696
type: SpeciesReference
stoichiometry: 1.0
species: 419886

449683
type: SpeciesReference
stoichiometry: 1.0
species: 420846

449671
type: SpeciesReference
stoichiometry: 1.0
species: 419926

424905
type: Reaction
kinetic law: 449757
product: 449745
reactant: 449733
reactant: 449720
notes: Same rates as PKA-phosph-I1
fast: false
reversible: true

449757
type: KineticLaw
local parameters: 449442
local parameters: 449441
notes: k1*AC_slash_cAMP_minus_PDE*PKA_minus_active-k2*PKA_minus_active_slash_phosph_minus_PDE_slash_phosph_minus_PDE_cplx

449442
type: LocalParameter
units: 443196
value: 5.4E-14

449441
type: LocalParameter
units: 443280
value: 9.000045E-15

449745
type: SpeciesReference
stoichiometry: 1.0
species: 419946

449733
type: SpeciesReference
stoichiometry: 1.0
species: 419886

449720
type: SpeciesReference
stoichiometry: 1.0
species: 421466

423845
type: Reaction
kinetic law: 446817
product: 446805
reactant: 446793
notes: Reverse reaction is for turning off the synthesis.
fast: false
reversible: true

446817
type: KineticLaw
local parameters: 449338
local parameters: 449335
notes: kf*MKP3_slash_nucleotides-kb*MKP3_slash_MKP3_synthesis

449338
type: LocalParameter
units: 443196
value: 1.5E-18

449335
type: LocalParameter
units: 443196
value: 1.5E-21

446805
type: SpeciesReference
stoichiometry: 1.0
species: 421786

446793
type: SpeciesReference
stoichiometry: 1.0
species: 422206

422885
type: Reaction
kinetic law: 444686
product: 444674
reactant: 444662
reactant: 444650
notes: Assume the binding is fast and limited only by the amount of Ras* available. So kf=kb/[craf-1] If kb is 1/sec, then kf = 1/0.2 uM = 1/(0.2 * 6e5) = 8.3e-6 Later: Raise it by 10 X to 4e-5 From Hallberg et al JBC 269:6 3913-3916 1994, 3% of cellular Raf is complexed with Ras. So we raise kb 4x to 4 This step needed to memb-anchor and activate Raf: Leevers et al Nature 369 411-414 May 16, 2003 Changed Ras and Raf to synaptic levels, an increase of about 2x for each. To maintain the percentage of complexed Raf, reduced the kf by 2.4 fold to 10.
fast: false
reversible: true

444686
type: KineticLaw
local parameters: 449146
local parameters: 449143
notes: kf*MAPK_slash_craf_minus_1_star_*Ras_slash_GTP_minus_Ras-kb*MAPK_slash_Raf_star__minus_GTP_minus_Ras

449146
type: LocalParameter
units: 443196
value: 7.5E-16

449143
type: LocalParameter
units: 443280
value: 1.499985E-14

444674
type: SpeciesReference
stoichiometry: 1.0
species: 419446

444662
type: SpeciesReference
stoichiometry: 1.0
species: 419726

444650
type: SpeciesReference
stoichiometry: 1.0
species: 419266

423705
type: Reaction
kinetic law: 446527
product: 446515
reactant: 446503
reactant: 446491
notes: Half-max at around 3nM = kb/kf from fig 5 in Feinstein et al PNAS USA 88 10173-10177 1991 kf = kb/1800 = 5.56e-4 kb Ofer\'s thesis data indicates it is more like 2 nM. kf = kb/1200 = 8.33e-4
fast: false
reversible: true

446527
type: KineticLaw
local parameters: 449310
local parameters: 449307
notes: kf*AC_slash_AC2*Gs_minus_alpha-kb*AC_slash_AC2_minus_Gs

449310
type: LocalParameter
units: 443196
value: 1.5E-15

449307
type: LocalParameter
units: 443280
value: 7.499925E-13

446515
type: SpeciesReference
stoichiometry: 1.0
species: 421366

446503
type: SpeciesReference
stoichiometry: 1.0
species: 421626

446491
type: SpeciesReference
stoichiometry: 1.0
species: 421386

425345
type: Reaction
kinetic law: 450849
product: 450836
reactant: 450824
reactant: 450811
notes: See Cohen et al
fast: false
reversible: true

450849
type: KineticLaw
local parameters: 449482
local parameters: 449481
notes: k1*CaMKII_slash_CaMK_minus_thr306*PP1_minus_active-k2*PP1_minus_active_slash_Deph_minus_thr306_slash_Deph_minus_thr306_cplx

449482
type: LocalParameter
units: 443196
value: 2.1E-15

449481
type: LocalParameter
units: 443280
value: 5.147955E-16

450836
type: SpeciesReference
stoichiometry: 1.0
species: 420606

450824
type: SpeciesReference
stoichiometry: 1.0
species: 420546

450811
type: SpeciesReference
stoichiometry: 1.0
species: 420446

422905
type: Reaction
kinetic law: 444734
product: 444722
reactant: 444710
reactant: 444698
notes: SoS/GEF is present at 50 nM ie 3e4/cell. BetaGamma maxes out at 9e4. Assume we have 1/3 of the GEF active when the BetaGamma is 1.5e4. so 1e4 * kb = 2e4 * 1.5e4 * kf, so kf/kb = 3e-5. The rate of this equil should be reasonably fast, say 1/sec
fast: false
reversible: true

444734
type: KineticLaw
local parameters: 449150
local parameters: 449147
notes: kf*BetaGamma*Ras_slash_inact_minus_GEF-kb*Ras_slash_GEF_minus_Gprot_minus_bg

449150
type: LocalParameter
units: 443196
value: 1.5E-15

449147
type: LocalParameter
units: 443280
value: 9.000045E-15

444722
type: SpeciesReference
stoichiometry: 1.0
species: 419626

444710
type: SpeciesReference
stoichiometry: 1.0
species: 419666

444698
type: SpeciesReference
stoichiometry: 1.0
species: 419066

423825
type: Reaction
kinetic law: 446781
product: 446769
reactant: 446757
fast: false
reversible: true

446781
type: KineticLaw
local parameters: 449334
local parameters: 449331
notes: kf*MAPK_star_^2-kb*MKP3_slash_nuc_MAPK_star_

449334
type: LocalParameter
units: 443196
value: 1.5E-18

449331
type: LocalParameter
units: 443280
value: 3.75003E-19

446769
type: SpeciesReference
stoichiometry: 1.0
species: 421686

446757
type: SpeciesReference
stoichiometry: 2.0
species: 418846

422245
type: Species
notes: Amino acids for MKP3 synthesis.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 418386

424205
type: Reaction
kinetic law: 447653
product: 447641
product: 447629
reactant: 447617
fast: false
reversible: false

447653
type: KineticLaw
local parameters: 449380
notes: k3*MAPK_star__slash_MAPK_star__minus_feedback_slash_MAPK_star__minus_feedback_cplx

449380
type: LocalParameter
units: 443196
value: 1.5E-14

447641
type: SpeciesReference
stoichiometry: 1.0
species: 418846

447629
type: SpeciesReference
stoichiometry: 1.0
species: 419326

447617
type: SpeciesReference
stoichiometry: 1.0
species: 418886

426085
type: Reaction
kinetic law: 452641
product: 452629
reactant: 452617
reactant: 452605
fast: false
reversible: true

452641
type: KineticLaw
local parameters: 449557
local parameters: 449556
notes: k1*MKP3_slash_MKP3_AA*MKP3_slash_MKP3_synthesis-k2*MKP3_slash_MKP3_synthesis_slash_kenz_slash_kenz_cplx

449557
type: LocalParameter
units: 443196
value: 6.0E-17

449556
type: LocalParameter
units: 443280
value: 3.75003E-16

452629
type: SpeciesReference
stoichiometry: 1.0
species: 421806

452617
type: SpeciesReference
stoichiometry: 1.0
species: 421786

452605
type: SpeciesReference
stoichiometry: 1.0
species: 422245