MODEL9081220742
type: SBMLModel
reaction: 971210
species: 964800
reaction: 970610
reaction: 970790
reaction: 969590
species: 966730
species: 966990
species: 965610
reaction: 969070
reaction: 970810
reaction: 969630
reaction: 967570
species: 966470
species: 966570
species: 964680
reaction: 970630
reaction: 971190
reaction: 968210
species: 965690
reaction: 968770
species: 966390
reaction: 968810
reaction: 968130
reaction: 970990
species: 966510
reaction: 969370
species: 964720
species: 964281
reaction: 969410
species: 966350
reaction: 967930
reaction: 969210
species: 964920
reaction: 967370
reaction: 968630
reaction: 970410
notes: This is a network model of many pathways present at the neuronal synapse. The network has properties of temporal tuning as well as steady-state computational properties. In its default form the network is bistable.Bhalla US Biophys J. 2004 Aug;87(2):745-53 This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
reaction: 968150
species: 965411
species: 965730
species: 964521
species: 965470
reaction: 968970
species: 964340
species: 966810
rule: 967330
reaction: 969830
reaction: 969570
reaction: 970770
species: 963961
species: 964500
reaction: 969610
reaction: 968290
reaction: 970390
reaction: 968550
reaction: 970590
species: 966150
length unit: length
reaction: 969490
reaction: 968750
species: 965750
reaction: 969150
species: 964101
reaction: 969350
species: 966750
species: 964641
species: 965120
reaction: 967490
reaction: 967690
species: 966930
reaction: 969170
species: 965670
reaction: 967910
species: 964381
species: 964481
reaction: 971030
species: 965830
species: 966250
species: 965040

971210
type: Reaction
kinetic law: 239498
product: 239485
product: 239472
reactant: 239460
fast: false
reversible: false

239498
type: KineticLaw
local parameters: 510121
notes: k3*AC_slash_PDE1_slash_PDE1_slash_PDE1_cplx

510121
type: LocalParameter
units: 230126
value: 1.667E-12

230150
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND

230138
type: SBMLUnit
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE

239485
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stoichiometry: 1.0
species: 966910

966910
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 2.0
initial amount: NaN
in compartment: 963861

963861
type: Compartment
constant: true
size: 1.0E-12
spatial dimensions: 3.0

239472
type: SpeciesReference
stoichiometry: 1.0
species: 966790

966790
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 325490.0
initial amount: NaN
in compartment: 963881

963881
type: Compartment
constant: true
size: 1.6667E-18
spatial dimensions: 3.0

239460
type: SpeciesReference
stoichiometry: 1.0
species: 966930

966930
type: Species
constant: false
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initial amount: NaN
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964800
type: Species
constant: false
boundary condition: false
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initial concentration: 0.0
initial amount: NaN
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970610
type: Reaction
kinetic law: 238044
product: 238032
reactant: 238020
reactant: 238008
fast: false
reversible: true

238044
type: KineticLaw
local parameters: 510054
local parameters: 510052
notes: k1*CaMKII_slash_CaMKII_star__star__star_*PP1_minus_active-k2*PP1_minus_active_slash_Deph_minus_thr305_slash_Deph_minus_thr305_cplx

510054
type: LocalParameter
units: 230126
value: 1.4E-12

510052
type: LocalParameter
units: 230211
value: 3.432E-13

230247
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND

230235
type: SBMLUnit
exponent: -1.0
scale: -6
multipler: 1.0
kind: MOLE

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type: SBMLUnit
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scale: 0
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kind: LITRE

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species: 965930

965930
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238020
type: SpeciesReference
stoichiometry: 1.0
species: 965910

965910
type: Species
constant: false
boundary condition: false
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initial concentration: 1.8
initial amount: NaN
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238008
type: SpeciesReference
stoichiometry: 1.0
species: 965770

965770
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
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970790
type: Reaction
kinetic law: 238479
product: 238467
product: 238455
reactant: 238442
fast: false
reversible: false

238479
type: KineticLaw
local parameters: 510074
notes: k3*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_neurogranin_slash_dephosph_neurogranin_cplx

510074
type: LocalParameter
units: 230126
value: 6.7E-13

238467
type: SpeciesReference
stoichiometry: 1.0
species: 967270

967270
type: Species
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

238455
type: SpeciesReference
stoichiometry: 1.0
species: 966070

966070
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 10.0
initial amount: NaN
in compartment: 963861

238442
type: SpeciesReference
stoichiometry: 1.0
species: 966130

966130
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

969590
type: Reaction
kinetic law: 235551
product: 235539
product: 235527
reactant: 235515
fast: false
reversible: false

235551
type: KineticLaw
local parameters: 509960
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx

509960
type: LocalParameter
units: 230126
value: 1.5E-13

235539
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stoichiometry: 1.0
species: 964740

964740
type: Species
constant: false
boundary condition: false
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initial concentration: 0.0
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235527
type: SpeciesReference
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species: 964720

964720
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

235515
type: SpeciesReference
stoichiometry: 1.0
species: 964780

964780
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

966730
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

966990
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

965610
type: Species
constant: false
boundary condition: false
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initial concentration: 0.1
initial amount: NaN
in compartment: 963861

969070
type: Reaction
kinetic law: 234248
product: 234236
product: 234224
reactant: 234212
fast: false
reversible: false

234248
type: KineticLaw
local parameters: 509915
notes: k3*PKC_minus_active_slash_PKC_minus_phosph_minus_neurogranin_slash_PKC_minus_phosph_minus_neurogranin_cplx

509915
type: LocalParameter
units: 230126
value: 5.8E-13

234236
type: SpeciesReference
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species: 967210

967210
type: Species
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.02
initial amount: NaN
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234224
type: SpeciesReference
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species: 966050

966050
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

234212
type: SpeciesReference
stoichiometry: 1.0
species: 964221

964221
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

970810
type: Reaction
kinetic law: 238527
product: 238515
reactant: 238503
reactant: 238491
fast: false
reversible: true

238527
type: KineticLaw
local parameters: 510076
local parameters: 510075
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

510076
type: LocalParameter
units: 230126
value: 1.36E-12

510075
type: LocalParameter
units: 230211
value: 3.42E-13

238515
type: SpeciesReference
stoichiometry: 1.0
species: 966150

966150
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

238503
type: SpeciesReference
stoichiometry: 1.0
species: 967270

238491
type: SpeciesReference
stoichiometry: 1.0
species: 966210

966210
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.001
initial amount: NaN
in compartment: 963861

969630
type: Reaction
kinetic law: 235650
product: 235637
product: 235625
reactant: 235612
fast: false
reversible: false

235650
type: KineticLaw
local parameters: 509963
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx

509963
type: LocalParameter
units: 230126
value: 1.5E-13

235637
type: SpeciesReference
stoichiometry: 1.0
species: 964740

235625
type: SpeciesReference
stoichiometry: 1.0
species: 964421

964421
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

235612
type: SpeciesReference
stoichiometry: 1.0
species: 964800

967570
type: Reaction
kinetic law: 230759
product: 230747
reactant: 230735
reactant: 230723
notes: Leslie and Channon BBA 1045 (1990) 261-270 fig6 pp267.
fast: false
reversible: true

230759
type: KineticLaw
local parameters: 509624
local parameters: 509622
notes: kf*PLA2_slash_PLA2_minus_cytosolic*Ca-kb*PLA2_slash_PLA2_minus_Ca_star_

509624
type: LocalParameter
units: 230126
value: 1.0E-13

509622
type: LocalParameter
units: 230211
value: 1.00002E-12

230747
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species: 964301

964301
type: Species
constant: false
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230735
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stoichiometry: 1.0
species: 967190

967190
type: Species
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.08
initial amount: NaN
in compartment: 963861

230723
type: SpeciesReference
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species: 964281

964281
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.4
initial amount: NaN
in compartment: 963861

966470
type: Species
constant: false
boundary condition: false
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initial concentration: 0.5
initial amount: NaN
in compartment: 963861

966570
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

964680
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.18
initial amount: NaN
in compartment: 963861

970630
type: Reaction
kinetic law: 238092
product: 238080
product: 238068
reactant: 238056
fast: false
reversible: false

238092
type: KineticLaw
local parameters: 510056
notes: k3*PP1_minus_active_slash_Deph_minus_thr305_slash_Deph_minus_thr305_cplx

510056
type: LocalParameter
units: 230126
value: 3.5E-13

238080
type: SpeciesReference
stoichiometry: 1.0
species: 965910

238068
type: SpeciesReference
stoichiometry: 1.0
species: 965790

965790
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

238056
type: SpeciesReference
stoichiometry: 1.0
species: 965930

971190
type: Reaction
kinetic law: 239448
product: 239436
reactant: 239424
reactant: 239412
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

239448
type: KineticLaw
local parameters: 510120
local parameters: 510119
notes: k1*cAMP*AC_slash_PDE1-k2*AC_slash_PDE1_slash_PDE1_slash_PDE1_cplx

510120
type: LocalParameter
units: 230126
value: 6.67E-12

510119
type: LocalParameter
units: 230211
value: 2.1E-13

239436
type: SpeciesReference
stoichiometry: 1.0
species: 966930

239424
type: SpeciesReference
stoichiometry: 1.0
species: 966910

239412
type: SpeciesReference
stoichiometry: 1.0
species: 966650

966650
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

968210
type: Reaction
kinetic law: 232188
product: 232176
reactant: 232164
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

232188
type: KineticLaw
local parameters: 509752
local parameters: 509750
notes: kf*EGFR_slash_L_dot_EGFR-kb*EGFR_slash_Internal_L_dot_EGFR

509752
type: LocalParameter
units: 230126
value: 3.3E-16

509750
type: LocalParameter
units: 230126
value: 2.0E-15

232176
type: SpeciesReference
stoichiometry: 1.0
species: 965510

965510
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

232164
type: SpeciesReference
stoichiometry: 1.0
species: 965411

965411
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

965690
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

968770
type: Reaction
kinetic law: 233550
product: 233538
reactant: 233526
reactant: 233514
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

233550
type: KineticLaw
local parameters: 509868
local parameters: 509866
notes: kf*PKA_minus_active*PKA_slash_PKA_minus_inhibitor-kb*PKA_slash_inhibited_minus_PKA

509868
type: LocalParameter
units: 230126
value: 1.0E-12

509866
type: LocalParameter
units: 230211
value: 6.0E-11

233538
type: SpeciesReference
stoichiometry: 1.0
species: 966630

966630
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

233526
type: SpeciesReference
stoichiometry: 1.0
species: 966610

966610
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.25
initial amount: NaN
in compartment: 963861

233514
type: SpeciesReference
stoichiometry: 1.0
species: 965275

965275
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

966390
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

968810
type: Reaction
kinetic law: 233634
product: 233622
reactant: 233610
notes: Random rate.
fast: false
reversible: true

233634
type: KineticLaw
local parameters: 509876
local parameters: 509874
notes: kf*AC_slash_AC2_star_-kb*AC_slash_AC2

509876
type: LocalParameter
units: 230126
value: 0.0

509874
type: LocalParameter
units: 230126
value: 1.0E-13

233622
type: SpeciesReference
stoichiometry: 1.0
species: 966750

966750
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.015
initial amount: NaN
in compartment: 963861

233610
type: SpeciesReference
stoichiometry: 1.0
species: 966710

966710
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

968130
type: Reaction
kinetic law: 232032
product: 232020
reactant: 232008
reactant: 231996
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
fast: false
reversible: true

232032
type: KineticLaw
local parameters: 509736
local parameters: 509734
notes: kf*Ras_slash_inact_minus_GEF*CaM_minus_Ca4-kb*Ras_slash_CaM_minus_GEF

509736
type: LocalParameter
units: 230126
value: 1.0E-12

509734
type: LocalParameter
units: 230211
value: 6.0E-11

232020
type: SpeciesReference
stoichiometry: 1.0
species: 965263

965263
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

232008
type: SpeciesReference
stoichiometry: 1.0
species: 965330

965330
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

231996
type: SpeciesReference
stoichiometry: 1.0
species: 965100

965100
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.1
initial amount: NaN
in compartment: 963861

970990
type: Reaction
kinetic law: 238964
product: 238952
product: 238940
reactant: 238928
fast: false
reversible: false

238964
type: KineticLaw
local parameters: 510089
notes: k3*CaNAB_minus_Ca4_slash_dephosph_inhib1_noCaM_slash_dephosph_inhib1_noCaM_cplx

510089
type: LocalParameter
units: 230126
value: 3.4E-14

238952
type: SpeciesReference
stoichiometry: 1.0
species: 966330

966330
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

238940
type: SpeciesReference
stoichiometry: 1.0
species: 966190

966190
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.8
initial amount: NaN
in compartment: 963861

238928
type: SpeciesReference
stoichiometry: 1.0
species: 966350

966350
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

966510
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

969370
type: Reaction
kinetic law: 234984
product: 234972
reactant: 234959
reactant: 234947
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

234984
type: KineticLaw
local parameters: 509941
local parameters: 509940
notes: k1*PLA2_slash_PLA2_minus_cytosolic*MAPK_star_-k2*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx

509941
type: LocalParameter
units: 230126
value: 8.0E-11

509940
type: LocalParameter
units: 230211
value: 3.9E-12

234972
type: SpeciesReference
stoichiometry: 1.0
species: 964440

964440
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

234959
type: SpeciesReference
stoichiometry: 1.0
species: 964421

234947
type: SpeciesReference
stoichiometry: 1.0
species: 964281

969410
type: Reaction
kinetic law: 235081
product: 235068
reactant: 235056
reactant: 235044
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

235081
type: KineticLaw
local parameters: 509944
local parameters: 509943
notes: k1*MAPK_slash_craf_minus_1_star_*MAPK_star_-k2*MAPK_star__slash_MAPK_star__minus_feedback_slash_MAPK_star__minus_feedback_cplx

509944
type: LocalParameter
units: 230126
value: 4.0E-11

509943
type: LocalParameter
units: 230211
value: 1.95E-12

235068
type: SpeciesReference
stoichiometry: 1.0
species: 964441

964441
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

235056
type: SpeciesReference
stoichiometry: 1.0
species: 964421

235044
type: SpeciesReference
stoichiometry: 1.0
species: 964660

964660
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

967930
type: Reaction
kinetic law: 231571
product: 231558
reactant: 231546
reactant: 231534
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

231571
type: KineticLaw
local parameters: 509696
local parameters: 509694
notes: kf*Gq_slash_G_minus_GDP*Gq_slash_Rec_minus_Glu-kb*Gq_slash_Rec_minus_Glu_minus_Gq

509696
type: LocalParameter
units: 230126
value: 1.0E-16

509694
type: LocalParameter
units: 230211
value: 6.0E-15

231558
type: SpeciesReference
stoichiometry: 1.0
species: 964620

964620
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

231546
type: SpeciesReference
stoichiometry: 1.0
species: 964581

964581
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

231534
type: SpeciesReference
stoichiometry: 1.0
species: 964561

964561
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 963861

969210
type: Reaction
kinetic law: 234597
product: 234585
reactant: 234573
reactant: 234561
notes: 10 X raise oct 22 12 X further raise oct 24 to allow for correct conc of enzyme
fast: false
reversible: true

234597
type: KineticLaw
local parameters: 509926
local parameters: 509925
notes: k1*PLA2_slash_APC*PLA2_slash_PIP2_minus_PLA2_star_-k2*PLA2_slash_PIP2_minus_PLA2_star__slash_kenz_slash_kenz_cplx

509926
type: LocalParameter
units: 230126
value: 4.416E-11

509925
type: LocalParameter
units: 230211
value: 2.76E-12

234585
type: SpeciesReference
stoichiometry: 1.0
species: 964340

964340
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

234573
type: SpeciesReference
stoichiometry: 1.0
species: 964321

964321
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

234561
type: SpeciesReference
stoichiometry: 1.0
species: 967010

967010
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: 963861

964920
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

967370
type: Reaction
kinetic law: 230320
product: 230308
reactant: 230295
reactant: 230283
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

230320
type: KineticLaw
local parameters: 509591
local parameters: 509590
notes: kf*PKC_slash_PKC_minus_cytosolic*Ca-kb*PKC_slash_PKC_minus_Ca

509591
type: LocalParameter
units: 230126
value: 5.0E-13

509590
type: LocalParameter
units: 230211
value: 6.0E-13

230308
type: SpeciesReference
stoichiometry: 1.0
species: 963901

963901
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.72083333333333E-17
initial amount: NaN
in compartment: 963861

230295
type: SpeciesReference
stoichiometry: 1.0
species: 967190

230283
type: SpeciesReference
stoichiometry: 1.0
species: 964101

964101
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 963861

968630
type: Reaction
kinetic law: 233210
product: 233197
reactant: 233185
reactant: 233173
fast: false
reversible: true

233210
type: KineticLaw
local parameters: 509840
local parameters: 509838
notes: kf*CaM_minus_Ca4*CaNAB_minus_Ca4-kb*PP2B_slash_CaMCa4_minus_CaNAB

509840
type: LocalParameter
units: 230126
value: 1.0E-12

509838
type: LocalParameter
units: 230211
value: 6.0E-10

233197
type: SpeciesReference
stoichiometry: 1.0
species: 966450

966450
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

233185
type: SpeciesReference
stoichiometry: 1.0
species: 966330

233173
type: SpeciesReference
stoichiometry: 1.0
species: 965330

970410
type: Reaction
kinetic law: 237558
product: 237546
reactant: 237534
reactant: 237522
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

237558
type: KineticLaw
local parameters: 510037
local parameters: 510036
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

510037
type: LocalParameter
units: 230126
value: 2.4E-11

510036
type: LocalParameter
units: 230211
value: 2.64084E-13

237546
type: SpeciesReference
stoichiometry: 1.0
species: 965830

965830
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

237534
type: SpeciesReference
stoichiometry: 1.0
species: 967230

967230
type: Species
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

237522
type: SpeciesReference
stoichiometry: 1.0
species: 965790

968150
type: Reaction
kinetic law: 232068
product: 232056
reactant: 232044
fast: false
reversible: true

232068
type: KineticLaw
local parameters: 509740
local parameters: 509738
notes: kf*Ras_slash_inact_minus_GEF_star_-kb*Ras_slash_inact_minus_GEF

509740
type: LocalParameter
units: 230126
value: 0.0

509738
type: LocalParameter
units: 230126
value: 1.0E-12

232056
type: SpeciesReference
stoichiometry: 1.0
species: 965100

232044
type: SpeciesReference
stoichiometry: 1.0
species: 965260

965260
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

965730
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

964521
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

965470
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 963861

968970
type: Reaction
kinetic law: 234008
product: 233996
reactant: 233984
reactant: 233972
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

234008
type: KineticLaw
local parameters: 509905
local parameters: 509903
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

509905
type: LocalParameter
units: 230126
value: 1.6E-11

509903
type: LocalParameter
units: 230211
value: 6.0E-12

233996
type: SpeciesReference
stoichiometry: 1.0
species: 964181

964181
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

233984
type: SpeciesReference
stoichiometry: 1.0
species: 967210

233972
type: SpeciesReference
stoichiometry: 1.0
species: 965220

965220
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.002
initial amount: NaN
in compartment: 963861

966810
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

969830
type: Reaction
kinetic law: 236132
product: 236120
product: 236108
reactant: 236096
fast: false
reversible: false

509981
type: LocalParameter
units: 230126
value: 6.0E-12

236120
type: SpeciesReference
stoichiometry: 1.0
species: 964960

964960
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.224
initial amount: NaN
in compartment: 963861

236108
type: SpeciesReference
stoichiometry: 1.0
species: 964641

964641
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.2
initial amount: NaN
in compartment: 963861

236096
type: SpeciesReference
stoichiometry: 1.0
species: 964980

964980
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

969570
type: Reaction
kinetic law: 235503
product: 235490
reactant: 235478
reactant: 235466
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

235503
type: KineticLaw
local parameters: 509958
local parameters: 509956
notes: k1*MAPK_slash_MAPK*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx

509958
type: LocalParameter
units: 230126
value: 6.0E-13

509956
type: LocalParameter
units: 230211
value: 1.62E-11

235490
type: SpeciesReference
stoichiometry: 1.0
species: 964780

235478
type: SpeciesReference
stoichiometry: 1.0
species: 964740

235466
type: SpeciesReference
stoichiometry: 1.0
species: 964700

964700
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.36
initial amount: NaN
in compartment: 963861

970770
type: Reaction
kinetic law: 238429
product: 238417
reactant: 238405
reactant: 238393
notes: From Seki et al ABB 316(2):673-679
fast: false
reversible: true

238429
type: KineticLaw
local parameters: 510073
local parameters: 510072
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

510073
type: LocalParameter
units: 230126
value: 2.67E-12

510072
type: LocalParameter
units: 230211
value: 3.336E-13

238417
type: SpeciesReference
stoichiometry: 1.0
species: 966130

238405
type: SpeciesReference
stoichiometry: 1.0
species: 967270

238393
type: SpeciesReference
stoichiometry: 1.0
species: 966050

963961
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.3896E-17
initial amount: NaN
in compartment: 963861

964500
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

969610
type: Reaction
kinetic law: 235599
product: 235587
reactant: 235575
reactant: 235563
notes: Rate consts same as for MAPKKtyr.
fast: false
reversible: true

235599
type: KineticLaw
local parameters: 509962
local parameters: 509961
notes: k1*MAPK_slash_MAPK_minus_tyr*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx

509962
type: LocalParameter
units: 230126
value: 6.0E-13

509961
type: LocalParameter
units: 230211
value: 1.62E-11

235587
type: SpeciesReference
stoichiometry: 1.0
species: 964800

235575
type: SpeciesReference
stoichiometry: 1.0
species: 964740

235563
type: SpeciesReference
stoichiometry: 1.0
species: 964720

968290
type: Reaction
kinetic law: 232371
product: 232359
reactant: 232347
reactant: 232335
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

232371
type: KineticLaw
local parameters: 509768
local parameters: 509766
notes: kf*Sos_slash_Grb2*Sos_slash_Sos-kb*Sos_slash_Sos_dot_Grb2

509768
type: LocalParameter
units: 230126
value: 1.68E-14

509766
type: LocalParameter
units: 230211
value: 2.50002E-14

232359
type: SpeciesReference
stoichiometry: 1.0
species: 965570

965570
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

232347
type: SpeciesReference
stoichiometry: 1.0
species: 965610

232335
type: SpeciesReference
stoichiometry: 1.0
species: 965550

965550
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 963861

970390
type: Reaction
modifier: 237498
reversible: false
product: 237474
fast: false
product: 237486
reactant: 237462
kinetic law: 237510
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.

237474
type: SpeciesReference
stoichiometry: 1.0
species: 964121

964121
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

237486
type: SpeciesReference
stoichiometry: 1.0
species: 964461

964461
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.73
initial amount: NaN
in compartment: 963861

237462
type: SpeciesReference
stoichiometry: 1.0
species: 967110

967110
type: Species
constant: true
boundary condition: true
has only substance units: false
initial concentration: 10.0
initial amount: NaN
in compartment: 963861

237510
type: KineticLaw
local parameters: 510035
local parameters: 510034
notes: kcat*PLC_g_slash_Ca_dot_PLC_g_star_*PIP2/(Km+PIP2)

510035
type: LocalParameter
units: 230090
value: 19.7916666666667

230114
type: SBMLUnit
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE

230102
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE

510034
type: LocalParameter
units: 230126
value: 5.7E-11

968550
type: Reaction
kinetic law: 233016
product: 233003
reactant: 232991
reactant: 232979
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

233016
type: KineticLaw
local parameters: 509824
local parameters: 509822
notes: kf*Ca^2*PP2B_slash_CaNAB_minus_Ca2-kb*CaNAB_minus_Ca4

509824
type: LocalParameter
units: 230126
value: 1.0E-12

509822
type: LocalParameter
units: 230162
value: 3.6E-12

230198
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND

230186
type: SBMLUnit
exponent: -2.0
scale: -6
multipler: 1.0
kind: MOLE

230174
type: SBMLUnit
exponent: 3.0
scale: 0
multipler: 1.0
kind: LITRE

233003
type: SpeciesReference
stoichiometry: 1.0
species: 966330

232991
type: SpeciesReference
stoichiometry: 1.0
species: 966390

232979
type: SpeciesReference
stoichiometry: 2.0
species: 967190

970590
type: Reaction
kinetic law: 237996
product: 237984
product: 237972
reactant: 237959
fast: false
reversible: false

237996
type: KineticLaw
local parameters: 510050
notes: k3*PP1_minus_active_slash_Deph_minus_thr286_slash_Deph_minus_thr286_cplx

510050
type: LocalParameter
units: 230126
value: 3.5E-13

237984
type: SpeciesReference
stoichiometry: 1.0
species: 965910

237972
type: SpeciesReference
stoichiometry: 1.0
species: 965730

237959
type: SpeciesReference
stoichiometry: 1.0
species: 964760

964760
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

969490
type: Reaction
kinetic law: 235276
product: 235264
reactant: 235251
reactant: 235238
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

235276
type: KineticLaw
local parameters: 509950
local parameters: 509949
notes: k1*PIP2*PLCbeta_slash_PLC_minus_Ca-k2*PLCbeta_slash_PLC_minus_Ca_slash_PLC_minus_Ca_slash_PLC_minus_Ca_cplx

509950
type: LocalParameter
units: 230126
value: 4.0E-11

509949
type: LocalParameter
units: 230211
value: 2.52E-12

235264
type: SpeciesReference
stoichiometry: 1.0
species: 964500

235251
type: SpeciesReference
stoichiometry: 1.0
species: 964481

964481
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

235238
type: SpeciesReference
stoichiometry: 1.0
species: 967110

968750
type: Reaction
kinetic law: 233501
product: 233489
product: 233477
reactant: 233465
fast: false
reversible: true

233501
type: KineticLaw
local parameters: 509864
local parameters: 509862
notes: kf*PKA_slash_R2C_minus_cAMP4-kb*PKA_minus_active*PKA_slash_R2_minus_cAMP4

509864
type: LocalParameter
units: 230211
value: 1.8E-11

509862
type: LocalParameter
units: 230126
value: 6.0E-11

233489
type: SpeciesReference
stoichiometry: 1.0
species: 966590

966590
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

233477
type: SpeciesReference
stoichiometry: 1.0
species: 965275

233465
type: SpeciesReference
stoichiometry: 1.0
species: 966570

965750
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

969150
type: Reaction
kinetic law: 234453
product: 234441
product: 234429
reactant: 234417
fast: false
reversible: false

234453
type: KineticLaw
local parameters: 509921
notes: k3*PKC_minus_active_slash_phosph_minus_AC2_slash_phosph_minus_AC2_cplx

509921
type: LocalParameter
units: 230126
value: 4.0E-12

234441
type: SpeciesReference
stoichiometry: 1.0
species: 967210

234429
type: SpeciesReference
stoichiometry: 1.0
species: 966710

234417
type: SpeciesReference
stoichiometry: 1.0
species: 964261

964261
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

969350
type: Reaction
kinetic law: 234935
product: 234923
product: 234911
reactant: 234899
fast: false
reversible: false

234935
type: KineticLaw
local parameters: 509939
notes: k3*PLA2_slash_PLA2_star__minus_Ca_slash_kenz_slash_kenz_cplx

509939
type: LocalParameter
units: 230126
value: 1.2E-10

234923
type: SpeciesReference
stoichiometry: 1.0
species: 964381

964381
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

234911
type: SpeciesReference
stoichiometry: 1.0
species: 964141

964141
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

234899
type: SpeciesReference
stoichiometry: 1.0
species: 964401

964401
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

965120
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

967490
type: Reaction
kinetic law: 230563
product: 230551
reactant: 230538
notes: Initial basal levels were set by kf = 1, kb = 20. In model, though, the basal levels of PKC activity are higher.
fast: false
reversible: true

230563
type: KineticLaw
local parameters: 509608
local parameters: 509606
notes: kf*PKC_slash_PKC_minus_cytosolic-kb*PKC_slash_PKC_minus_basal_star_

509608
type: LocalParameter
units: 230126
value: 5.0E-11

509606
type: LocalParameter
units: 230126
value: 1.0E-12

230551
type: SpeciesReference
stoichiometry: 1.0
species: 964001

964001
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

230538
type: SpeciesReference
stoichiometry: 1.0
species: 964101

967690
type: Reaction
kinetic law: 231025
product: 231013
reactant: 231001
fast: false
reversible: true

231025
type: KineticLaw
local parameters: 509648
local parameters: 509646
notes: kf*PLA2_slash_PLA2_star_-kb*PLA2_slash_PLA2_minus_cytosolic

509648
type: LocalParameter
units: 230126
value: 0.0

509646
type: LocalParameter
units: 230126
value: 1.7E-13

231013
type: SpeciesReference
stoichiometry: 1.0
species: 964281

231001
type: SpeciesReference
stoichiometry: 1.0
species: 964420

964420
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

969170
type: Reaction
kinetic law: 234501
product: 234489
reactant: 234477
reactant: 234465
notes: 10 x raise oct22 12 x oct 24, set k2 = 4 * k3
fast: false
reversible: true

234501
type: KineticLaw
local parameters: 509923
local parameters: 509922
notes: k1*PLA2_slash_APC*PLA2_slash_PLA2_minus_Ca_star_-k2*PLA2_slash_PLA2_minus_Ca_star__slash_kenz_slash_kenz_cplx

509923
type: LocalParameter
units: 230126
value: 2.16E-11

509922
type: LocalParameter
units: 230211
value: 1.35E-12

234489
type: SpeciesReference
stoichiometry: 1.0
species: 964320

964320
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

234477
type: SpeciesReference
stoichiometry: 1.0
species: 964301

234465
type: SpeciesReference
stoichiometry: 1.0
species: 967010

965670
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

967910
type: Reaction
kinetic law: 231522
product: 231510
reactant: 231498
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

231522
type: KineticLaw
local parameters: 509692
local parameters: 509690
notes: kf*G_star_GTP-kb*G_star_GDP

509692
type: LocalParameter
units: 230126
value: 0.0

509690
type: LocalParameter
units: 230126
value: 1.33E-14

231510
type: SpeciesReference
stoichiometry: 1.0
species: 964560

964560
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

231498
type: SpeciesReference
stoichiometry: 1.0
species: 964541

964541
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

971030
type: Reaction
kinetic law: 239061
modifier: 239049
product: 239037
reactant: 239024
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

239061
type: KineticLaw
local parameters: 510097
local parameters: 510095
notes: kcat*AC_slash_AC2_star_*AC_slash_ATP/(Km+AC_slash_ATP)

510097
type: LocalParameter
units: 230090
value: 20.1149425287356

510095
type: LocalParameter
units: 230126
value: 7.0E-12

239037
type: SpeciesReference
stoichiometry: 1.0
species: 966650

239024
type: SpeciesReference
stoichiometry: 1.0
species: 967170

967170
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: 963861

966250
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

965040
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

964880
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

969990
type: Reaction
kinetic law: 236519
product: 236506
product: 236494
reactant: 236482
fast: false
reversible: false

236519
type: KineticLaw
local parameters: 509993
notes: k3*Ras_slash_GEF_minus_Gprot_minus_bg_slash_GEF_minus_bg_act_minus_ras_slash_GEF_minus_bg_act_minus_ras_cplx

509993
type: LocalParameter
units: 230126
value: 2.0E-14

236506
type: SpeciesReference
stoichiometry: 1.0
species: 965060

965060
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

236494
type: SpeciesReference
stoichiometry: 1.0
species: 965160

965160
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

236482
type: SpeciesReference
stoichiometry: 1.0
species: 965080

965080
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

968330
type: Reaction
kinetic law: 232468
product: 232456
reactant: 232444
reactant: 232432
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

232468
type: KineticLaw
local parameters: 509776
local parameters: 509774
notes: kf*Ca*PLC_g_slash_PLC_G_star_-kb*PLC_g_slash_Ca_dot_PLC_g_star_

509776
type: LocalParameter
units: 230126
value: 1.0E-11

509774
type: LocalParameter
units: 230211
value: 1.2E-11

232456
type: SpeciesReference
stoichiometry: 1.0
species: 965690

232444
type: SpeciesReference
stoichiometry: 1.0
species: 965650

965650
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

232432
type: SpeciesReference
stoichiometry: 1.0
species: 967190

969690
type: Reaction
kinetic law: 235796
product: 235784
reactant: 235772
reactant: 235760
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

235796
type: KineticLaw
local parameters: 509968
local parameters: 509967
notes: k1*MAPK_slash_MAPKK_minus_ser*MAPK_slash_Raf_minus_GTP_minus_Ras_star_-k2*MAPK_slash_Raf_minus_GTP_minus_Ras_star__slash_Raf_minus_GTP_minus_Ras_star__dot_2_slash_Raf_minus_GTP_minus_Ras_star__dot_2_cplx

509968
type: LocalParameter
units: 230126
value: 4.2E-13

509967
type: LocalParameter
units: 230211
value: 3.3E-12

235784
type: SpeciesReference
stoichiometry: 1.0
species: 964880

235772
type: SpeciesReference
stoichiometry: 1.0
species: 964840

964840
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

235760
type: SpeciesReference
stoichiometry: 1.0
species: 964820

964820
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

971050
type: Reaction
kinetic law: 239110
modifier: 239098
product: 239085
reactant: 239073
fast: false
reversible: false

239110
type: KineticLaw
local parameters: 510101
local parameters: 510099
notes: kcat*AC_slash_AC2_minus_Gs*AC_slash_ATP/(Km+AC_slash_ATP)

510101
type: LocalParameter
units: 230090
value: 20.0

510099
type: LocalParameter
units: 230126
value: 1.8E-11

239085
type: SpeciesReference
stoichiometry: 1.0
species: 966650

239073
type: SpeciesReference
stoichiometry: 1.0
species: 967170

970890
type: Reaction
kinetic law: 238722
product: 238710
reactant: 238698
reactant: 238685
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

238722
type: KineticLaw
local parameters: 510082
local parameters: 510081
notes: k1*PP1_slash_I1_star_*PP2A-k2*PP2A_slash_PP2A_minus_dephosph_minus_I1_slash_PP2A_minus_dephosph_minus_I1_cplx

510082
type: LocalParameter
units: 230126
value: 2.5E-11

510081
type: LocalParameter
units: 230211
value: 3.96E-12

238710
type: SpeciesReference
stoichiometry: 1.0
species: 966290

966290
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

238698
type: SpeciesReference
stoichiometry: 1.0
species: 966270

966270
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.12
initial amount: NaN
in compartment: 963861

238685
type: SpeciesReference
stoichiometry: 1.0
species: 966210

968610
type: Reaction
kinetic law: 233161
product: 233149
reactant: 233137
reactant: 233125
fast: false
reversible: true

233161
type: KineticLaw
local parameters: 509836
local parameters: 509834
notes: kf*CaM_minus_Ca3*CaNAB_minus_Ca4-kb*PP2B_slash_CaMCa3_minus_CaNAB

509836
type: LocalParameter
units: 230126
value: 1.0E-12

509834
type: LocalParameter
units: 230211
value: 2.238E-12

233149
type: SpeciesReference
stoichiometry: 1.0
species: 966410

966410
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

233137
type: SpeciesReference
stoichiometry: 1.0
species: 966330

233125
type: SpeciesReference
stoichiometry: 1.0
species: 966090

966090
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

969010
type: Reaction
kinetic law: 234104
product: 234092
reactant: 234080
reactant: 234068
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

234104
type: KineticLaw
local parameters: 509910
local parameters: 509908
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

509910
type: LocalParameter
units: 230126
value: 1.6E-11

509908
type: LocalParameter
units: 230211
value: 6.0E-12

234092
type: SpeciesReference
stoichiometry: 1.0
species: 964201

964201
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

234080
type: SpeciesReference
stoichiometry: 1.0
species: 967210

234068
type: SpeciesReference
stoichiometry: 1.0
species: 965100

968950
type: Reaction
kinetic law: 233960
product: 233948
product: 233936
reactant: 233924
fast: false
reversible: false

233960
type: KineticLaw
local parameters: 509902
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_raf_slash_PKC_minus_act_minus_raf_cplx

509902
type: LocalParameter
units: 230126
value: 4.0E-12

233948
type: SpeciesReference
stoichiometry: 1.0
species: 967210

233936
type: SpeciesReference
stoichiometry: 1.0
species: 964660

233924
type: SpeciesReference
stoichiometry: 1.0
species: 964161

964161
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

965240
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

969550
type: Reaction
kinetic law: 235453
product: 235440
product: 235427
product: 235414
reactant: 235401
fast: false
reversible: false

235453
type: KineticLaw
local parameters: 509954
notes: k3*PLCbeta_slash_PLC_minus_Ca_minus_Gq_slash_PLCb_minus_Ca_minus_Gq_slash_PLCb_minus_Ca_minus_Gq_cplx

509954
type: LocalParameter
units: 230126
value: 4.8E-11

235440
type: SpeciesReference
stoichiometry: 1.0
species: 964501

964501
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

235427
type: SpeciesReference
stoichiometry: 1.0
species: 964461

235414
type: SpeciesReference
stoichiometry: 1.0
species: 964121

235401
type: SpeciesReference
stoichiometry: 1.0
species: 964520

964520
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

970750
type: Reaction
kinetic law: 238381
product: 238369
product: 238357
reactant: 238345
fast: false
reversible: false

238381
type: KineticLaw
local parameters: 510071
notes: k3*PP1_minus_active_slash_Deph_thr286b_slash_Deph_thr286b_cplx

510071
type: LocalParameter
units: 230126
value: 3.5E-13

238369
type: SpeciesReference
stoichiometry: 1.0
species: 965910

238357
type: SpeciesReference
stoichiometry: 1.0
species: 965710

965710
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 70.0
initial amount: NaN
in compartment: 963861

238345
type: SpeciesReference
stoichiometry: 1.0
species: 965990

965990
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

969030
type: Reaction
kinetic law: 234152
product: 234140
product: 234128
reactant: 234116
fast: false
reversible: false

234152
type: KineticLaw
local parameters: 509912
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_GEF_slash_PKC_minus_act_minus_GEF_cplx

509912
type: LocalParameter
units: 230126
value: 4.0E-12

234140
type: SpeciesReference
stoichiometry: 1.0
species: 967210

234128
type: SpeciesReference
stoichiometry: 1.0
species: 965120

234116
type: SpeciesReference
stoichiometry: 1.0
species: 964201

969770
type: Reaction
kinetic law: 235988
product: 235976
reactant: 235964
reactant: 235952
notes: See MKP1-tyr-deph
fast: false
reversible: true

235988
type: KineticLaw
local parameters: 509974
local parameters: 509973
notes: k1*MAPK_star_*MKP_minus_1-k2*MKP_minus_1_slash_MKP1_minus_thr_minus_deph_slash_MKP1_minus_thr_minus_deph_cplx

509974
type: LocalParameter
units: 230126
value: 4.0E-12

509973
type: LocalParameter
units: 230211
value: 7.5E-11

235976
type: SpeciesReference
stoichiometry: 1.0
species: 964940

964940
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

235964
type: SpeciesReference
stoichiometry: 1.0
species: 964900

964900
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0024
initial amount: NaN
in compartment: 963861

235952
type: SpeciesReference
stoichiometry: 1.0
species: 964421

970230
type: Reaction
kinetic law: 237100
product: 237088
product: 237076
reactant: 237064
fast: false
reversible: false

237100
type: KineticLaw
local parameters: 510020
notes: k3*PKA_minus_active_slash_phosph_minus_PDE_slash_phosph_minus_PDE_cplx

510020
type: LocalParameter
units: 230126
value: 9.0E-12

237088
type: SpeciesReference
stoichiometry: 1.0
species: 965275

237076
type: SpeciesReference
stoichiometry: 1.0
species: 966870

966870
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

237064
type: SpeciesReference
stoichiometry: 1.0
species: 965310

965310
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

967530
type: Reaction
kinetic law: 230662
product: 230650
reactant: 230638
reactant: 230626
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

230662
type: KineticLaw
local parameters: 509616
local parameters: 509614
notes: kf*PKC_slash_PKC_minus_cytosolic*DAG-kb*PKC_slash_PKC_minus_DAG

509616
type: LocalParameter
units: 230126
value: 1.0E-13

509614
type: LocalParameter
units: 230211
value: 6.0E-16

230650
type: SpeciesReference
stoichiometry: 1.0
species: 964061

964061
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.16101666666667E-16
initial amount: NaN
in compartment: 963861

230638
type: SpeciesReference
stoichiometry: 1.0
species: 964121

230626
type: SpeciesReference
stoichiometry: 1.0
species: 964101

969470
type: Reaction
kinetic law: 235226
product: 235214
product: 235202
reactant: 235189
fast: false
reversible: false

235226
type: KineticLaw
local parameters: 509948
notes: k3*MAPK_star__slash_phosph_Sos_slash_phosph_Sos_cplx

509948
type: LocalParameter
units: 230126
value: 1.0E-11

235214
type: SpeciesReference
stoichiometry: 1.0
species: 964421

235202
type: SpeciesReference
stoichiometry: 1.0
species: 965590

965590
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

235189
type: SpeciesReference
stoichiometry: 1.0
species: 964460

964460
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

966430
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

966530
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

965950
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

965370
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

970030
type: Reaction
kinetic law: 236615
product: 236603
product: 236591
reactant: 236579
fast: false
reversible: false

236615
type: KineticLaw
local parameters: 509996
notes: k3*Ras_slash_GEF_star__slash_GEF_star__minus_act_minus_ras_slash_GEF_star__minus_act_minus_ras_cplx

509996
type: LocalParameter
units: 230126
value: 2.0E-14

236603
type: SpeciesReference
stoichiometry: 1.0
species: 965120

236591
type: SpeciesReference
stoichiometry: 1.0
species: 965160

236579
type: SpeciesReference
stoichiometry: 1.0
species: 965140

965140
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

971150
type: Reaction
kinetic law: 239351
product: 239339
reactant: 239327
reactant: 239315
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

239351
type: KineticLaw
local parameters: 510117
local parameters: 510116
notes: k1*cAMP*AC_slash_cAMP_minus_PDE_star_-k2*AC_slash_cAMP_minus_PDE_star__slash_PDE_star__slash_PDE_star__cplx

510117
type: LocalParameter
units: 230126
value: 8.0E-11

510116
type: LocalParameter
units: 230211
value: 5.04E-12

239339
type: SpeciesReference
stoichiometry: 1.0
species: 966890

966890
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

239327
type: SpeciesReference
stoichiometry: 1.0
species: 966870

239315
type: SpeciesReference
stoichiometry: 1.0
species: 966650

969890
type: Reaction
kinetic law: 236276
product: 236264
reactant: 236252
reactant: 236240
fast: false
reversible: true

509986
type: LocalParameter
units: 230126
value: 2.5E-11

509985
type: LocalParameter
units: 230211
value: 1.98E-12

236264
type: SpeciesReference
stoichiometry: 1.0
species: 965020

965020
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

236252
type: SpeciesReference
stoichiometry: 1.0
species: 964960

236240
type: SpeciesReference
stoichiometry: 1.0
species: 964820

967550
type: Reaction
kinetic law: 230710
product: 230698
reactant: 230686
reactant: 230674
notes: Reduced kf to 0.66X to match Shinomura et al data. Initial: kf = 3.3333e-9 New: 2e-9 Newer: 2e-8 kb was 0.2 now 2.
fast: false
reversible: true

230710
type: KineticLaw
local parameters: 509620
local parameters: 509618
notes: kf*PKC_slash_PKC_minus_DAG*AA-kb*PKC_slash_PKC_minus_DAG_minus_AA

509620
type: LocalParameter
units: 230126
value: 2.0E-12

509618
type: LocalParameter
units: 230211
value: 1.8E-14

230698
type: SpeciesReference
stoichiometry: 1.0
species: 964081

964081
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 2.51883333333333E-19
initial amount: NaN
in compartment: 963861

230686
type: SpeciesReference
stoichiometry: 1.0
species: 964141

230674
type: SpeciesReference
stoichiometry: 1.0
species: 964061

970090
type: Reaction
kinetic law: 236759
product: 236747
reactant: 236735
reactant: 236723
notes: Kinetics same as GEF-bg_act-ras
fast: false
reversible: true

236759
type: KineticLaw
local parameters: 510003
local parameters: 510001
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

510003
type: LocalParameter
units: 230126
value: 8.0E-14

510001
type: LocalParameter
units: 230211
value: 1.98E-13

236747
type: SpeciesReference
stoichiometry: 1.0
species: 965272

965272
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

236735
type: SpeciesReference
stoichiometry: 1.0
species: 965263

236723
type: SpeciesReference
stoichiometry: 1.0
species: 965180

965180
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.2
initial amount: NaN
in compartment: 963861

968730
type: Reaction
kinetic law: 233453
product: 233441
product: 233429
reactant: 233417
notes: This has to be fast, as the activation of PKA by cAMP is also fast. kf was 10
fast: false
reversible: true

233453
type: KineticLaw
local parameters: 509860
local parameters: 509858
notes: kf*PKA_slash_R2C2_minus_cAMP4-kb*PKA_minus_active*PKA_slash_R2C_minus_cAMP4

509860
type: LocalParameter
units: 230211
value: 1.8E-11

509858
type: LocalParameter
units: 230126
value: 6.0E-11

233441
type: SpeciesReference
stoichiometry: 1.0
species: 966570

233429
type: SpeciesReference
stoichiometry: 1.0
species: 965275

233417
type: SpeciesReference
stoichiometry: 1.0
species: 966550

966550
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

965290
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

967130
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: 963861

969330
type: Reaction
kinetic law: 234887
product: 234875
reactant: 234863
reactant: 234851
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

234887
type: KineticLaw
local parameters: 509938
local parameters: 509937
notes: k1*PLA2_slash_APC*PLA2_slash_PLA2_star__minus_Ca-k2*PLA2_slash_PLA2_star__minus_Ca_slash_kenz_slash_kenz_cplx

509938
type: LocalParameter
units: 230126
value: 4.8E-10

509937
type: LocalParameter
units: 230211
value: 3.0E-11

234875
type: SpeciesReference
stoichiometry: 1.0
species: 964401

234863
type: SpeciesReference
stoichiometry: 1.0
species: 964381

234851
type: SpeciesReference
stoichiometry: 1.0
species: 967010

971170
type: Reaction
kinetic law: 239400
product: 239387
product: 239375
reactant: 239363
fast: false
reversible: false

239400
type: KineticLaw
local parameters: 510118
notes: k3*AC_slash_cAMP_minus_PDE_star__slash_PDE_star__slash_PDE_star__cplx

510118
type: LocalParameter
units: 230126
value: 2.0E-11

239387
type: SpeciesReference
stoichiometry: 1.0
species: 966870

239375
type: SpeciesReference
stoichiometry: 1.0
species: 966790

239363
type: SpeciesReference
stoichiometry: 1.0
species: 966890

967830
type: Reaction
kinetic law: 231341
product: 231329
reactant: 231317
reactant: 231305
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

231341
type: KineticLaw
local parameters: 509676
local parameters: 509674
notes: kf*Ca*PLCbeta_slash_PLC_minus_Gq-kb*PLCbeta_slash_PLC_minus_Ca_minus_Gq

509676
type: LocalParameter
units: 230126
value: 1.0E-12

509674
type: LocalParameter
units: 230211
value: 3.0E-11

231329
type: SpeciesReference
stoichiometry: 1.0
species: 964501

231317
type: SpeciesReference
stoichiometry: 1.0
species: 964521

231305
type: SpeciesReference
stoichiometry: 1.0
species: 967190

964241
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

967670
type: Reaction
kinetic law: 230989
product: 230977
reactant: 230965
reactant: 230953
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

230989
type: KineticLaw
local parameters: 509644
local parameters: 509642
notes: kf*PLA2_slash_PLA2_star_*Ca-kb*PLA2_slash_PLA2_star__minus_Ca

509644
type: LocalParameter
units: 230126
value: 1.0E-13

509642
type: LocalParameter
units: 230211
value: 6.0E-12

230977
type: SpeciesReference
stoichiometry: 1.0
species: 964381

230965
type: SpeciesReference
stoichiometry: 1.0
species: 967190

230953
type: SpeciesReference
stoichiometry: 1.0
species: 964420

966310
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

968110
type: Reaction
kinetic law: 231983
product: 231971
reactant: 231959
notes: Assume a reasonably good rate for dephosphorylating it, 1/sec
fast: false
reversible: true

231983
type: KineticLaw
local parameters: 509732
local parameters: 509730
notes: kf*Ras_slash_GAP_star_-kb*Ras_slash_GAP

509732
type: LocalParameter
units: 230126
value: 0.0

509730
type: LocalParameter
units: 230126
value: 1.0E-13

231971
type: SpeciesReference
stoichiometry: 1.0
species: 965220

231959
type: SpeciesReference
stoichiometry: 1.0
species: 965200

965200
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

965970
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

965430
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

969670
type: Reaction
kinetic law: 235748
product: 235736
product: 235724
reactant: 235712
fast: false
reversible: false

235748
type: KineticLaw
local parameters: 509966
notes: k3*MAPK_slash_Raf_minus_GTP_minus_Ras_star__slash_Raf_minus_GTP_minus_Ras_star__dot_1_slash_Raf_minus_GTP_minus_Ras_star__dot_1_cplx

509966
type: LocalParameter
units: 230126
value: 1.05E-13

235736
type: SpeciesReference
stoichiometry: 1.0
species: 964840

235724
type: SpeciesReference
stoichiometry: 1.0
species: 964820

235712
type: SpeciesReference
stoichiometry: 1.0
species: 964860

964860
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

970870
type: Reaction
kinetic law: 238673
product: 238661
product: 238649
reactant: 238637
fast: false
reversible: false

238673
type: KineticLaw
local parameters: 510080
notes: k3*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_minus_PP1_minus_I_star__slash_dephosph_minus_PP1_minus_I_star__cplx

510080
type: LocalParameter
units: 230126
value: 3.4E-13

238661
type: SpeciesReference
stoichiometry: 1.0
species: 967270

238649
type: SpeciesReference
stoichiometry: 1.0
species: 966250

238637
type: SpeciesReference
stoichiometry: 1.0
species: 966170

966170
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

970730
type: Reaction
kinetic law: 238333
product: 238321
reactant: 238309
reactant: 238297
fast: false
reversible: true

238333
type: KineticLaw
local parameters: 510069
local parameters: 510067
notes: k1*CaMKII_slash_CaMKII_minus_thr286*PP1_minus_active-k2*PP1_minus_active_slash_Deph_thr286b_slash_Deph_thr286b_cplx

510069
type: LocalParameter
units: 230126
value: 1.4E-12

510067
type: LocalParameter
units: 230211
value: 3.432E-13

238321
type: SpeciesReference
stoichiometry: 1.0
species: 965990

238309
type: SpeciesReference
stoichiometry: 1.0
species: 965910

238297
type: SpeciesReference
stoichiometry: 1.0
species: 965790

963921
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 4.91366666666667E-18
initial amount: NaN
in compartment: 963861

967450
type: Reaction
kinetic law: 230489
product: 230477
reactant: 230465
reactant: 230452
notes: Schaechter and Benowitz We have to increase Kf for conc scaling Changed kf to 2e-9 on Sept 19, 94. This gives better match.
fast: false
reversible: true

230489
type: KineticLaw
local parameters: 509600
local parameters: 509598
notes: kf*PKC_slash_PKC_minus_Ca*AA-kb*PKC_slash_PKC_minus_Ca_minus_AA_star_

509600
type: LocalParameter
units: 230126
value: 1.0E-13

509598
type: LocalParameter
units: 230211
value: 1.2E-15

230477
type: SpeciesReference
stoichiometry: 1.0
species: 963941

963941
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.75E-16
initial amount: NaN
in compartment: 963861

230465
type: SpeciesReference
stoichiometry: 1.0
species: 964141

230452
type: SpeciesReference
stoichiometry: 1.0
species: 963901

968250
type: Reaction
kinetic law: 232286
product: 232274
reactant: 232262
reactant: 232250
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

232286
type: KineticLaw
local parameters: 509760
local parameters: 509758
notes: kf*Sos_slash_Sos_star_*Sos_slash_Grb2-kb*Sos_slash_Sos_star__dot_Grb2

509760
type: LocalParameter
units: 230126
value: 1.68E-14

509758
type: LocalParameter
units: 230211
value: 2.50002E-14

232274
type: SpeciesReference
stoichiometry: 1.0
species: 965530

965530
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

232262
type: SpeciesReference
stoichiometry: 1.0
species: 965550

232250
type: SpeciesReference
stoichiometry: 1.0
species: 965590

967250
type: Species
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

966850
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

970130
type: Reaction
kinetic law: 236857
product: 236845
reactant: 236832
reactant: 236820
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

236857
type: KineticLaw
local parameters: 510008
local parameters: 510006
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

510008
type: LocalParameter
units: 230126
value: 3.6E-11

510006
type: LocalParameter
units: 230211
value: 6.0E-12

236845
type: SpeciesReference
stoichiometry: 1.0
species: 965290

236832
type: SpeciesReference
stoichiometry: 1.0
species: 965275

236820
type: SpeciesReference
stoichiometry: 1.0
species: 965100

969750
type: Reaction
kinetic law: 235940
product: 235928
product: 235916
reactant: 235904
fast: false
reversible: false

235940
type: KineticLaw
local parameters: 509972
notes: k3*MKP_minus_1_slash_MKP1_minus_tyr_minus_deph_slash_MKP1_minus_tyr_minus_deph_cplx

509972
type: LocalParameter
units: 230126
value: 1.0E-12

235928
type: SpeciesReference
stoichiometry: 1.0
species: 964900

235916
type: SpeciesReference
stoichiometry: 1.0
species: 964700

235904
type: SpeciesReference
stoichiometry: 1.0
species: 964920

964041
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 8.46316666666667E-23
initial amount: NaN
in compartment: 963861

968270
type: Reaction
kinetic law: 232323
product: 232310
reactant: 232298
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

232323
type: KineticLaw
local parameters: 509764
local parameters: 509762
notes: kf*Sos_slash_Sos_star_-kb*Sos_slash_Sos

509764
type: LocalParameter
units: 230126
value: 0.0

509762
type: LocalParameter
units: 230126
value: 1.0E-15

232310
type: SpeciesReference
stoichiometry: 1.0
species: 965610

232298
type: SpeciesReference
stoichiometry: 1.0
species: 965590

969450
type: Reaction
kinetic law: 235177
product: 235165
reactant: 235153
reactant: 235141
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

235177
type: KineticLaw
local parameters: 509947
local parameters: 509946
notes: k1*Sos_slash_Sos*MAPK_star_-k2*MAPK_star__slash_phosph_Sos_slash_phosph_Sos_cplx

509947
type: LocalParameter
units: 230126
value: 4.0E-11

509946
type: LocalParameter
units: 230211
value: 1.95E-11

235165
type: SpeciesReference
stoichiometry: 1.0
species: 964460

235153
type: SpeciesReference
stoichiometry: 1.0
species: 964421

235141
type: SpeciesReference
stoichiometry: 1.0
species: 965610

968870
type: Reaction
kinetic law: 233779
product: 233767
reactant: 233755
reactant: 233743
notes: kb/kf = 1.2 nM so kf = kb/720 = 1.3888 * kb.
fast: false
reversible: true

233779
type: KineticLaw
local parameters: 509888
local parameters: 509886
notes: kf*Gs_minus_alpha*AC_slash_AC2_star_-kb*AC_slash_AC2_star__minus_Gs

509888
type: LocalParameter
units: 230126
value: 1.0E-12

509886
type: LocalParameter
units: 230211
value: 8.3328E-10

233767
type: SpeciesReference
stoichiometry: 1.0
species: 966810

233755
type: SpeciesReference
stoichiometry: 1.0
species: 966710

233743
type: SpeciesReference
stoichiometry: 1.0
species: 966990

970370
type: Reaction
product: 237426
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.
modifier: 237438
kinetic law: 237450
reversible: false
fast: false
product: 237413
reactant: 237401

237426
type: SpeciesReference
stoichiometry: 1.0
species: 964461

237450
type: KineticLaw
local parameters: 510033
local parameters: 510032
notes: kcat*PLC_g_slash_Ca_dot_PLC_g*PIP2/(Km+PIP2)

510033
type: LocalParameter
units: 230090
value: 97.2222222222222

510032
type: LocalParameter
units: 230126
value: 1.4E-11

237413
type: SpeciesReference
stoichiometry: 1.0
species: 964121

237401
type: SpeciesReference
stoichiometry: 1.0
species: 967110

968530
type: Reaction
kinetic law: 232919
product: 232907
reactant: 232894
reactant: 232882
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

232919
type: KineticLaw
local parameters: 509816
local parameters: 509814
notes: kf*PP1_slash_I1_star_*PP1_minus_active-kb*PP1_slash_PP1_minus_I1_star_

509816
type: LocalParameter
units: 230126
value: 1.0E-13

509814
type: LocalParameter
units: 230211
value: 4.9998E-10

232907
type: SpeciesReference
stoichiometry: 1.0
species: 966230

966230
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

232894
type: SpeciesReference
stoichiometry: 1.0
species: 965910

232882
type: SpeciesReference
stoichiometry: 1.0
species: 966210

964701
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

967650
type: Reaction
kinetic law: 230941
product: 230929
reactant: 230917
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

230941
type: KineticLaw
local parameters: 509640
local parameters: 509638
notes: kf*AA-kb*PLA2_slash_APC

509640
type: LocalParameter
units: 230126
value: 0.0

509638
type: LocalParameter
units: 230126
value: 4.0E-13

230929
type: SpeciesReference
stoichiometry: 1.0
species: 967010

230917
type: SpeciesReference
stoichiometry: 1.0
species: 964141

969130
type: Reaction
kinetic law: 234405
product: 234393
reactant: 234381
reactant: 234369
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

234405
type: KineticLaw
local parameters: 509920
local parameters: 509919
notes: k1*AC_slash_AC2*PKC_minus_active-k2*PKC_minus_active_slash_phosph_minus_AC2_slash_phosph_minus_AC2_cplx

509920
type: LocalParameter
units: 230126
value: 1.6E-11

509919
type: LocalParameter
units: 230211
value: 6.0E-13

234393
type: SpeciesReference
stoichiometry: 1.0
species: 964261

234381
type: SpeciesReference
stoichiometry: 1.0
species: 967210

234369
type: SpeciesReference
stoichiometry: 1.0
species: 966750

968890
type: Reaction
kinetic law: 233816
product: 233803
reactant: 233791
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

233816
type: KineticLaw
local parameters: 509892
local parameters: 509890
notes: kf*AC_slash_cAMP_minus_PDE_star_-kb*AC_slash_cAMP_minus_PDE

509892
type: LocalParameter
units: 230126
value: 0.0

509890
type: LocalParameter
units: 230126
value: 1.0E-13

233803
type: SpeciesReference
stoichiometry: 1.0
species: 966830

966830
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.45
initial amount: NaN
in compartment: 963861

233791
type: SpeciesReference
stoichiometry: 1.0
species: 966870

968030
type: Reaction
kinetic law: 231826
product: 231814
reactant: 231802
reactant: 231790
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 (I don\'t....
fast: false
reversible: true

231826
type: KineticLaw
local parameters: 509716
local parameters: 509714
notes: kf*MAPK_slash_craf_minus_1_star_*Ras_slash_GTP_minus_Ras-kb*MAPK_slash_Raf_minus_GTP_minus_Ras_star_

509716
type: LocalParameter
units: 230126
value: 5.0E-13

509714
type: LocalParameter
units: 230211
value: 2.4E-11

231814
type: SpeciesReference
stoichiometry: 1.0
species: 964840

231802
type: SpeciesReference
stoichiometry: 1.0
species: 965160

231790
type: SpeciesReference
stoichiometry: 1.0
species: 964660

965630
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.82
initial amount: NaN
in compartment: 963861

967030
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: 963861

965000
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

970850
type: Reaction
kinetic law: 238625
product: 238613
reactant: 238601
reactant: 238589
fast: false
reversible: true

238625
type: KineticLaw
local parameters: 510079
local parameters: 510078
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

510079
type: LocalParameter
units: 230126
value: 1.36E-12

510078
type: LocalParameter
units: 230211
value: 3.42E-13

238613
type: SpeciesReference
stoichiometry: 1.0
species: 966170

238601
type: SpeciesReference
stoichiometry: 1.0
species: 967270

238589
type: SpeciesReference
stoichiometry: 1.0
species: 966230

968310
type: Reaction
kinetic law: 232420
product: 232407
reactant: 232396
reactant: 232383
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

232420
type: KineticLaw
local parameters: 509772
local parameters: 509770
notes: kf*PLC_g_slash_PLC_g*Ca-kb*PLC_g_slash_Ca_dot_PLC_g

509772
type: LocalParameter
units: 230126
value: 1.0E-11

509770
type: LocalParameter
units: 230211
value: 1.8E-10

232407
type: SpeciesReference
stoichiometry: 1.0
species: 965670

232396
type: SpeciesReference
stoichiometry: 1.0
species: 967190

232383
type: SpeciesReference
stoichiometry: 1.0
species: 965630

965870
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

967430
type: Reaction
kinetic law: 230440
product: 230428
reactant: 230416
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

230440
type: KineticLaw
local parameters: 509597
local parameters: 509596
notes: kf*PKC_slash_PKC_minus_Ca_minus_DAG-kb*PKC_slash_PKC_minus_DAG_minus_memb_star_

509597
type: LocalParameter
units: 230126
value: 1.0E-13

509596
type: LocalParameter
units: 230126
value: 1.0E-12

230428
type: SpeciesReference
stoichiometry: 1.0
species: 963981

963981
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 9.43516666666667E-21
initial amount: NaN
in compartment: 963861

230416
type: SpeciesReference
stoichiometry: 1.0
species: 964041

968390
type: Reaction
kinetic law: 232604
product: 232591
reactant: 232579
reactant: 232567
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

232604
type: KineticLaw
local parameters: 509788
local parameters: 509786
notes: kf*CaMKII_slash_CaMKII_minus_thr286*CaM_minus_Ca4-kb*CaMKII_slash_CaMKII_minus_thr286_star__minus_CaM

509788
type: LocalParameter
units: 230126
value: 1.0E-13

509786
type: LocalParameter
units: 230211
value: 1.0002E-9

232591
type: SpeciesReference
stoichiometry: 1.0
species: 965750

232579
type: SpeciesReference
stoichiometry: 1.0
species: 965330

232567
type: SpeciesReference
stoichiometry: 1.0
species: 965790

967710
type: Reaction
kinetic law: 231074
product: 231062
reactant: 231050
reactant: 231037
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

231074
type: KineticLaw
local parameters: 509652
local parameters: 509650
notes: kf*Ca*PLCbeta_slash_PLC-kb*PLCbeta_slash_PLC_minus_Ca

509652
type: LocalParameter
units: 230126
value: 1.0E-12

509650
type: LocalParameter
units: 230211
value: 3.0E-12

231062
type: SpeciesReference
stoichiometry: 1.0
species: 964481

231050
type: SpeciesReference
stoichiometry: 1.0
species: 964480

964480
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.8
initial amount: NaN
in compartment: 963861

231037
type: SpeciesReference
stoichiometry: 1.0
species: 967190

230271
type: SBMLUnit
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE

966370
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 963861

969730
type: Reaction
kinetic law: 235892
product: 235880
reactant: 235868
reactant: 235856
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
fast: false
reversible: true

235892
type: KineticLaw
local parameters: 509971
local parameters: 509970
notes: k1*MAPK_slash_MAPK_minus_tyr*MKP_minus_1-k2*MKP_minus_1_slash_MKP1_minus_tyr_minus_deph_slash_MKP1_minus_tyr_minus_deph_cplx

509971
type: LocalParameter
units: 230126
value: 4.0E-12

509970
type: LocalParameter
units: 230211
value: 7.5E-11

235880
type: SpeciesReference
stoichiometry: 1.0
species: 964920

235868
type: SpeciesReference
stoichiometry: 1.0
species: 964900

235856
type: SpeciesReference
stoichiometry: 1.0
species: 964720

964580
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.3
initial amount: NaN
in compartment: 963861

965490
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

968670
type: Reaction
kinetic law: 233308
product: 233295
reactant: 233283
reactant: 233271
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

233308
type: KineticLaw
local parameters: 509848
local parameters: 509846
notes: kf*PKA_slash_R2C2_minus_cAMP*cAMP-kb*PKA_slash_R2C2_minus_cAMP2

509848
type: LocalParameter
units: 230126
value: 3.3E-11

509846
type: LocalParameter
units: 230211
value: 5.4E-11

233295
type: SpeciesReference
stoichiometry: 1.0
species: 966510

233283
type: SpeciesReference
stoichiometry: 1.0
species: 966650

233271
type: SpeciesReference
stoichiometry: 1.0
species: 966490

966490
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

966010
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 20.0
initial amount: NaN
in compartment: 963861

971230
type: Reaction
kinetic law: 239546
product: 239534
reactant: 239522
reactant: 239510
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

239546
type: KineticLaw
local parameters: 510123
local parameters: 510122
notes: k1*cAMP*AC_slash_CaM_dot_PDE1-k2*AC_slash_CaM_dot_PDE1_slash_CaM_dot_PDE1_slash_CaM_dot_PDE1_cplx

510123
type: LocalParameter
units: 230126
value: 4.0E-11

510122
type: LocalParameter
units: 230211
value: 1.26E-12

239534
type: SpeciesReference
stoichiometry: 1.0
species: 966970

966970
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

239522
type: SpeciesReference
stoichiometry: 1.0
species: 966950

966950
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

239510
type: SpeciesReference
stoichiometry: 1.0
species: 966650

968190
type: Reaction
kinetic law: 232152
product: 232140
reactant: 232128
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

232152
type: KineticLaw
local parameters: 509748
local parameters: 509746
notes: kf*EGFR_slash_SHC_star_-kb*EGFR_slash_SHC

509748
type: LocalParameter
units: 230126
value: 0.0

509746
type: LocalParameter
units: 230126
value: 1.6667E-15

232140
type: SpeciesReference
stoichiometry: 1.0
species: 965470

232128
type: SpeciesReference
stoichiometry: 1.0
species: 965490

964341
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

967790
type: Reaction
kinetic law: 231245
product: 231233
product: 231221
reactant: 231208
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

231245
type: KineticLaw
local parameters: 509668
local parameters: 509666
notes: kf*PLCbeta_slash_PLC_minus_Ca_minus_Gq-kb*G_star_GDP*PLCbeta_slash_PLC_minus_Ca

509668
type: LocalParameter
units: 230211
value: 0.0

509666
type: LocalParameter
units: 230126
value: 1.33E-14

231233
type: SpeciesReference
stoichiometry: 1.0
species: 964481

231221
type: SpeciesReference
stoichiometry: 1.0
species: 964560

231208
type: SpeciesReference
stoichiometry: 1.0
species: 964501

967510
type: Reaction
kinetic law: 230613
product: 230601
reactant: 230588
reactant: 230576
notes: Raise kf from 1.667e-10 to 2e-10 to get better match to data.
fast: false
reversible: true

230613
type: KineticLaw
local parameters: 509612
local parameters: 509610
notes: kf*AA*PKC_slash_PKC_minus_cytosolic-kb*PKC_slash_PKC_minus_AA_star_

509612
type: LocalParameter
units: 230126
value: 1.0E-13

509610
type: LocalParameter
units: 230211
value: 1.2E-16

230601
type: SpeciesReference
stoichiometry: 1.0
species: 964021

964021
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.81333333333333E-17
initial amount: NaN
in compartment: 963861

230588
type: SpeciesReference
stoichiometry: 1.0
species: 964101

230576
type: SpeciesReference
stoichiometry: 1.0
species: 964141

970050
type: Reaction
kinetic law: 236663
product: 236651
reactant: 236639
reactant: 236627
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

236663
type: KineticLaw
local parameters: 509998
local parameters: 509997
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

509998
type: LocalParameter
units: 230126
value: 4.0E-11

509997
type: LocalParameter
units: 230211
value: 4.94856E-11

236651
type: SpeciesReference
stoichiometry: 1.0
species: 965240

236639
type: SpeciesReference
stoichiometry: 1.0
species: 965220

236627
type: SpeciesReference
stoichiometry: 1.0
species: 965160

967070
type: Species
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

968590
type: Reaction
kinetic law: 233112
product: 233100
reactant: 233088
reactant: 233076
notes: Disabled. See notes for PP2B7.g
fast: false
reversible: true

233112
type: KineticLaw
local parameters: 509832
local parameters: 509830
notes: kf*CaNAB_minus_Ca4*CaM_minus_TR2_minus_Ca2-kb*PP2B_slash_CaMCa2_minus_CANAB

509832
type: LocalParameter
units: 230126
value: 1.0E-12

509830
type: LocalParameter
units: 230211
value: 2.4E-13

233100
type: SpeciesReference
stoichiometry: 1.0
species: 966430

233088
type: SpeciesReference
stoichiometry: 1.0
species: 966110

966110
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

233076
type: SpeciesReference
stoichiometry: 1.0
species: 966330

968070
type: Reaction
kinetic law: 231911
product: 231899
reactant: 231887
fast: false
reversible: true

231911
type: KineticLaw
local parameters: 509724
local parameters: 509722
notes: kf*Ras_slash_GEF_star_-kb*Ras_slash_inact_minus_GEF

509724
type: LocalParameter
units: 230126
value: 0.0

509722
type: LocalParameter
units: 230126
value: 1.0E-12

231899
type: SpeciesReference
stoichiometry: 1.0
species: 965100

231887
type: SpeciesReference
stoichiometry: 1.0
species: 965120

967590
type: Reaction
kinetic law: 230808
product: 230795
reactant: 230783
reactant: 230771
fast: false
reversible: true

230808
type: KineticLaw
local parameters: 509628
local parameters: 509626
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_cytosolic-kb*PLA2_slash_PIP2_minus_PLA2_star_

509628
type: LocalParameter
units: 230126
value: 5.0E-13

509626
type: LocalParameter
units: 230211
value: 1.2E-15

230795
type: SpeciesReference
stoichiometry: 1.0
species: 964321

230783
type: SpeciesReference
stoichiometry: 1.0
species: 964281

230771
type: SpeciesReference
stoichiometry: 1.0
species: 967030

969870
type: Reaction
kinetic law: 236228
product: 236216
product: 236204
reactant: 236192
fast: false
reversible: false

509984
type: LocalParameter
units: 230126
value: 6.0E-12

236216
type: SpeciesReference
stoichiometry: 1.0
species: 964960

236204
type: SpeciesReference
stoichiometry: 1.0
species: 964820

236192
type: SpeciesReference
stoichiometry: 1.0
species: 965000

964360
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

970070
type: Reaction
kinetic law: 236711
product: 236699
product: 236687
reactant: 236675
fast: false
reversible: false

236711
type: KineticLaw
local parameters: 509999
notes: k3*Ras_slash_GAP_slash_GAP_minus_inact_minus_ras_slash_GAP_minus_inact_minus_ras_cplx

509999
type: LocalParameter
units: 230126
value: 1.0E-11

236699
type: SpeciesReference
stoichiometry: 1.0
species: 965220

236687
type: SpeciesReference
stoichiometry: 1.0
species: 965180

236675
type: SpeciesReference
stoichiometry: 1.0
species: 965240

967630
type: Reaction
kinetic law: 230905
product: 230893
reactant: 230881
reactant: 230869
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

230905
type: KineticLaw
local parameters: 509636
local parameters: 509634
notes: kf*DAG*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_DAG_minus_Ca_minus_PLA2_star_

509636
type: LocalParameter
units: 230126
value: 4.0E-12

509634
type: LocalParameter
units: 230211
value: 3.0E-15

230893
type: SpeciesReference
stoichiometry: 1.0
species: 964361

964361
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

230881
type: SpeciesReference
stoichiometry: 1.0
species: 964301

230869
type: SpeciesReference
stoichiometry: 1.0
species: 964121

968090
type: Reaction
kinetic law: 231947
product: 231935
reactant: 231923
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

231947
type: KineticLaw
local parameters: 509728
local parameters: 509726
notes: kf*Ras_slash_GTP_minus_Ras-kb*Ras_slash_GDP_minus_Ras

509728
type: LocalParameter
units: 230126
value: 0.0

509726
type: LocalParameter
units: 230126
value: 1.0E-16

231935
type: SpeciesReference
stoichiometry: 1.0
species: 965180

231923
type: SpeciesReference
stoichiometry: 1.0
species: 965160

969270
type: Reaction
kinetic law: 234743
product: 234730
product: 234718
reactant: 234706
fast: false
reversible: false

234743
type: KineticLaw
local parameters: 509930
notes: k3*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx

509930
type: LocalParameter
units: 230126
value: 3.6E-11

234730
type: SpeciesReference
stoichiometry: 1.0
species: 964341

234718
type: SpeciesReference
stoichiometry: 1.0
species: 964141

234706
type: SpeciesReference
stoichiometry: 1.0
species: 964360

968450
type: Reaction
kinetic law: 232737
product: 232725
reactant: 232713
reactant: 232701
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

232737
type: KineticLaw
local parameters: 509800
local parameters: 509798
notes: kf*CaM_minus_TR2_minus_Ca2*Ca-kb*CaM_minus_Ca3

509800
type: LocalParameter
units: 230126
value: 1.0E-11

509798
type: LocalParameter
units: 230211
value: 3.6E-12

232725
type: SpeciesReference
stoichiometry: 1.0
species: 966090

232713
type: SpeciesReference
stoichiometry: 1.0
species: 967190

232701
type: SpeciesReference
stoichiometry: 1.0
species: 966110

967990
type: Reaction
kinetic law: 231729
product: 231717
reactant: 231705
reactant: 231692
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

231729
type: KineticLaw
local parameters: 509708
local parameters: 509706
notes: kf*Gq_slash_G_minus_GDP*Gq_slash_mGluR-kb*Gq_slash_Rec_minus_Gq

509708
type: LocalParameter
units: 230126
value: 1.0E-12

509706
type: LocalParameter
units: 230211
value: 6.0E-13

231717
type: SpeciesReference
stoichiometry: 1.0
species: 964600

964600
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

231705
type: SpeciesReference
stoichiometry: 1.0
species: 964580

231692
type: SpeciesReference
stoichiometry: 1.0
species: 964561

966770
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

969810
type: Reaction
kinetic law: 236084
product: 236072
reactant: 236060
reactant: 236048
notes: See parent PPhosphatase2A for parms
fast: false
reversible: true

509979
type: LocalParameter
units: 230126
value: 2.5E-11

509977
type: LocalParameter
units: 230211
value: 1.98E-12

236072
type: SpeciesReference
stoichiometry: 1.0
species: 964980

236060
type: SpeciesReference
stoichiometry: 1.0
species: 964960

236048
type: SpeciesReference
stoichiometry: 1.0
species: 964660

968370
type: Reaction
kinetic law: 232555
product: 232543
reactant: 232531
reactant: 232518
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

232555
type: KineticLaw
local parameters: 509784
local parameters: 509782
notes: kf*CaM_minus_Ca4*CaMKII_slash_CaMKII-kb*CaMKII_slash_CaMKII_minus_CaM

509784
type: LocalParameter
units: 230126
value: 5.0E-12

509782
type: LocalParameter
units: 230211
value: 4.99998E-11

232543
type: SpeciesReference
stoichiometry: 1.0
species: 965730

232531
type: SpeciesReference
stoichiometry: 1.0
species: 965710

232518
type: SpeciesReference
stoichiometry: 1.0
species: 965330

968790
type: Reaction
kinetic law: 233598
product: 233586
reactant: 233574
reactant: 233562
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

233598
type: KineticLaw
local parameters: 509872
local parameters: 509870
notes: kf*CaM_minus_Ca4*AC_slash_AC1-kb*AC_slash_AC1_minus_CaM

509872
type: LocalParameter
units: 230126
value: 1.0E-12

509870
type: LocalParameter
units: 230211
value: 4.99998E-11

233586
type: SpeciesReference
stoichiometry: 1.0
species: 966670

966670
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

233574
type: SpeciesReference
stoichiometry: 1.0
species: 966690

966690
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.02
initial amount: NaN
in compartment: 963861

233562
type: SpeciesReference
stoichiometry: 1.0
species: 965330

969290
type: Reaction
kinetic law: 234791
product: 234779
reactant: 234767
reactant: 234755
notes: 10 X raise oct 22 12 X raise oct 24 + conversion to k2 =4 * k3
fast: false
reversible: true

234791
type: KineticLaw
local parameters: 509934
local parameters: 509932
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

509934
type: LocalParameter
units: 230126
value: 2.4E-10

509932
type: LocalParameter
units: 230211
value: 1.5E-11

234779
type: SpeciesReference
stoichiometry: 1.0
species: 964380

964380
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

234767
type: SpeciesReference
stoichiometry: 1.0
species: 964361

234755
type: SpeciesReference
stoichiometry: 1.0
species: 967010

969390
type: Reaction
kinetic law: 235032
product: 235020
product: 235008
reactant: 234996
fast: false
reversible: false

235032
type: KineticLaw
local parameters: 509942
notes: k3*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx

509942
type: LocalParameter
units: 230126
value: 2.0E-11

235020
type: SpeciesReference
stoichiometry: 1.0
species: 964421

235008
type: SpeciesReference
stoichiometry: 1.0
species: 964420

234996
type: SpeciesReference
stoichiometry: 1.0
species: 964440

965850
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

967410
type: Reaction
kinetic law: 230404
product: 230392
reactant: 230380
fast: false
reversible: true

230404
type: KineticLaw
local parameters: 509595
local parameters: 509594
notes: kf*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_memb_star_

509595
type: LocalParameter
units: 230126
value: 3.5026E-12

509594
type: LocalParameter
units: 230126
value: 1.2705E-12

230392
type: SpeciesReference
stoichiometry: 1.0
species: 963961

230380
type: SpeciesReference
stoichiometry: 1.0
species: 963901

970490
type: Reaction
kinetic law: 237754
product: 237741
reactant: 237729
reactant: 237717
notes: See Hanson and Schulman again, for afterburst rates of phosph.
fast: false
reversible: true

237754
type: KineticLaw
local parameters: 510043
local parameters: 510042
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

510043
type: LocalParameter
units: 230126
value: 2.4E-11

510042
type: LocalParameter
units: 230211
value: 1.71426E-13

237741
type: SpeciesReference
stoichiometry: 1.0
species: 965870

237729
type: SpeciesReference
stoichiometry: 1.0
species: 967250

237717
type: SpeciesReference
stoichiometry: 1.0
species: 965790

970570
type: Reaction
kinetic law: 237947
product: 237935
reactant: 237923
reactant: 237911
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

237947
type: KineticLaw
local parameters: 510049
local parameters: 510048
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

510049
type: LocalParameter
units: 230126
value: 1.4E-12

510048
type: LocalParameter
units: 230211
value: 3.432E-13

237935
type: SpeciesReference
stoichiometry: 1.0
species: 964760

237923
type: SpeciesReference
stoichiometry: 1.0
species: 965910

237911
type: SpeciesReference
stoichiometry: 1.0
species: 965750

967770
type: Reaction
kinetic law: 231196
product: 231184
reactant: 231171
reactant: 231159
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

231196
type: KineticLaw
local parameters: 509664
local parameters: 509662
notes: kf*G_star_GTP*PLCbeta_slash_PLC_minus_Ca-kb*PLCbeta_slash_PLC_minus_Ca_minus_Gq

509664
type: LocalParameter
units: 230126
value: 1.0E-12

509662
type: LocalParameter
units: 230211
value: 2.52E-11

231184
type: SpeciesReference
stoichiometry: 1.0
species: 964501

231171
type: SpeciesReference
stoichiometry: 1.0
species: 964481

231159
type: SpeciesReference
stoichiometry: 1.0
species: 964541

968230
type: Reaction
kinetic law: 232237
product: 232225
reactant: 232213
reactant: 232201
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

232237
type: KineticLaw
local parameters: 509756
local parameters: 509754
notes: kf*Sos_slash_Sos_dot_Grb2*EGFR_slash_SHC_star_-kb*Shc_star__dot_Sos_dot_Grb2

509756
type: LocalParameter
units: 230126
value: 1.0E-13

509754
type: LocalParameter
units: 230211
value: 4.9998E-13

232225
type: SpeciesReference
stoichiometry: 1.0
species: 965350

965350
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

232213
type: SpeciesReference
stoichiometry: 1.0
species: 965490

232201
type: SpeciesReference
stoichiometry: 1.0
species: 965570

968830
type: Reaction
kinetic law: 233683
product: 233671
reactant: 233659
reactant: 233646
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

233683
type: KineticLaw
local parameters: 509880
local parameters: 509878
notes: kf*AC_slash_AC2*Gs_minus_alpha-kb*AC_slash_AC2_minus_Gs

509880
type: LocalParameter
units: 230126
value: 1.0E-12

509878
type: LocalParameter
units: 230211
value: 4.99998E-10

233671
type: SpeciesReference
stoichiometry: 1.0
species: 966730

233659
type: SpeciesReference
stoichiometry: 1.0
species: 966990

233646
type: SpeciesReference
stoichiometry: 1.0
species: 966750

971090
type: Reaction
kinetic law: 239206
modifier: 239194
product: 239182
reactant: 239170
fast: false
reversible: false

239206
type: KineticLaw
local parameters: 510109
local parameters: 510107
notes: kcat*AC_slash_AC2_star__minus_Gs*AC_slash_ATP/(Km+AC_slash_ATP)

510109
type: LocalParameter
units: 230090
value: 60.0

510107
type: LocalParameter
units: 230126
value: 5.4E-11

239182
type: SpeciesReference
stoichiometry: 1.0
species: 966650

239170
type: SpeciesReference
stoichiometry: 1.0
species: 967170

967890
type: Reaction
kinetic law: 231486
product: 231474
reactant: 231462
reactant: 231450
notes: kf == kg3 = 1e-5 /cell/sec. As usual, there is no back-reaction kb = 0
fast: false
reversible: true

231486
type: KineticLaw
local parameters: 509688
local parameters: 509686
notes: kf*G_star_GDP*BetaGamma-kb*Gq_slash_G_minus_GDP

509688
type: LocalParameter
units: 230126
value: 0.0

509686
type: LocalParameter
units: 230211
value: 6.0E-12

231474
type: SpeciesReference
stoichiometry: 1.0
species: 964561

231462
type: SpeciesReference
stoichiometry: 1.0
species: 964540

964540
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

231450
type: SpeciesReference
stoichiometry: 1.0
species: 964560

968850
type: Reaction
kinetic law: 233731
product: 233719
reactant: 233707
reactant: 233695
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

233731
type: KineticLaw
local parameters: 509884
local parameters: 509882
notes: kf*Gs_minus_alpha*AC_slash_AC1-kb*AC_slash_AC1_minus_Gs

509884
type: LocalParameter
units: 230126
value: 1.0E-12

509882
type: LocalParameter
units: 230211
value: 1.26E-10

233719
type: SpeciesReference
stoichiometry: 1.0
species: 966770

233707
type: SpeciesReference
stoichiometry: 1.0
species: 966690

233695
type: SpeciesReference
stoichiometry: 1.0
species: 966990

968570
type: Reaction
kinetic law: 233064
product: 233052
reactant: 233040
reactant: 233028
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

233064
type: KineticLaw
local parameters: 509828
local parameters: 509826
notes: kf*PP2B_slash_CaNAB*Ca^2-kb*PP2B_slash_CaNAB_minus_Ca2

509828
type: LocalParameter
units: 230126
value: 1.0E-12

509826
type: LocalParameter
units: 230162
value: 1.0008E-8

233052
type: SpeciesReference
stoichiometry: 1.0
species: 966390

233040
type: SpeciesReference
stoichiometry: 2.0
species: 967190

233028
type: SpeciesReference
stoichiometry: 1.0
species: 966370

970210
type: Reaction
kinetic law: 237052
product: 237039
reactant: 237027
reactant: 237014
notes: Same rates as PKA-phosph-I1
fast: false
reversible: true

237052
type: KineticLaw
local parameters: 510018
local parameters: 510016
notes: k1*AC_slash_cAMP_minus_PDE*PKA_minus_active-k2*PKA_minus_active_slash_phosph_minus_PDE_slash_phosph_minus_PDE_cplx

510018
type: LocalParameter
units: 230126
value: 3.6E-11

510016
type: LocalParameter
units: 230211
value: 6.0E-12

237039
type: SpeciesReference
stoichiometry: 1.0
species: 965310

237027
type: SpeciesReference
stoichiometry: 1.0
species: 965275

237014
type: SpeciesReference
stoichiometry: 1.0
species: 966830

969910
type: Reaction
kinetic law: 236324
product: 236312
product: 236300
reactant: 236288
fast: false
reversible: false

509987
type: LocalParameter
units: 230126
value: 6.0E-12

236312
type: SpeciesReference
stoichiometry: 1.0
species: 964960

236300
type: SpeciesReference
stoichiometry: 1.0
species: 964680

236288
type: SpeciesReference
stoichiometry: 1.0
species: 965020

968010
type: Reaction
kinetic law: 231778
product: 231766
reactant: 231754
reactant: 231742
notes: The rate consts give a total binding affinity of only
fast: false
reversible: true

231778
type: KineticLaw
local parameters: 509712
local parameters: 509710
notes: kf*Gq_slash_Rec_minus_Gq*Gq_slash_mGluRAntag-kb*Gq_slash_Blocked_minus_rec_minus_Gq

509712
type: LocalParameter
units: 230126
value: 1.0E-14

509710
type: LocalParameter
units: 230211
value: 6.0E-11

231766
type: SpeciesReference
stoichiometry: 1.0
species: 964640

964640
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

231754
type: SpeciesReference
stoichiometry: 1.0
species: 967130

231742
type: SpeciesReference
stoichiometry: 1.0
species: 964600

968430
type: Reaction
kinetic law: 232689
product: 232677
reactant: 232665
reactant: 232653
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

232689
type: KineticLaw
local parameters: 509796
local parameters: 509794
notes: kf*CaM_slash_CaM*Ca^2-kb*CaM_minus_TR2_minus_Ca2

509796
type: LocalParameter
units: 230126
value: 7.2E-11

509794
type: LocalParameter
units: 230162
value: 7.2E-11

232677
type: SpeciesReference
stoichiometry: 1.0
species: 966110

232665
type: SpeciesReference
stoichiometry: 2.0
species: 967190

232653
type: SpeciesReference
stoichiometry: 1.0
species: 966010

967970
type: Reaction
product: 231644
product: 231656
reactant: 231632
reversible: true
product: 231668
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.
kinetic law: 231680
fast: false

231644
type: SpeciesReference
stoichiometry: 1.0
species: 964541

231656
type: SpeciesReference
stoichiometry: 1.0
species: 964540

231632
type: SpeciesReference
stoichiometry: 1.0
species: 964620

231668
type: SpeciesReference
stoichiometry: 1.0
species: 964581

231680
type: KineticLaw
local parameters: 509704
local parameters: 509702
notes: kf*Gq_slash_Rec_minus_Glu_minus_Gq-kb*G_star_GTP*BetaGamma*Gq_slash_Rec_minus_Glu

509704
type: LocalParameter
units: 230162
value: 0.0

509702
type: LocalParameter
units: 230126
value: 1.0E-14

970970
type: Reaction
kinetic law: 238916
product: 238904
reactant: 238891
reactant: 238879
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

238916
type: KineticLaw
local parameters: 510088
local parameters: 510087
notes: k1*PP1_slash_I1_star_*CaNAB_minus_Ca4-k2*CaNAB_minus_Ca4_slash_dephosph_inhib1_noCaM_slash_dephosph_inhib1_noCaM_cplx

510088
type: LocalParameter
units: 230126
value: 1.36E-13

510087
type: LocalParameter
units: 230211
value: 3.42E-14

238904
type: SpeciesReference
stoichiometry: 1.0
species: 966350

238891
type: SpeciesReference
stoichiometry: 1.0
species: 966330

238879
type: SpeciesReference
stoichiometry: 1.0
species: 966210

970690
type: Reaction
kinetic law: 238236
product: 238224
reactant: 238212
reactant: 238200
fast: false
reversible: true

238236
type: KineticLaw
local parameters: 510064
local parameters: 510062
notes: k1*CaMKII_slash_CaMKII_star__star__star_*PP1_minus_active-k2*PP1_minus_active_slash_Deph_minus_thr286c_slash_Deph_minus_thr286c_cplx

510064
type: LocalParameter
units: 230126
value: 1.4E-12

510062
type: LocalParameter
units: 230211
value: 3.432E-13

238224
type: SpeciesReference
stoichiometry: 1.0
species: 965970

238212
type: SpeciesReference
stoichiometry: 1.0
species: 965910

238200
type: SpeciesReference
stoichiometry: 1.0
species: 965770

968350
type: Reaction
kinetic law: 232505
product: 232493
reactant: 232481
fast: false
reversible: true

232505
type: KineticLaw
local parameters: 509780
local parameters: 509778
notes: kf*PLC_g_slash_Ca_dot_PLC_g_star_-kb*PLC_g_slash_Ca_dot_PLC_g

509780
type: LocalParameter
units: 230126
value: 0.0

509778
type: LocalParameter
units: 230126
value: 5.0E-14

232493
type: SpeciesReference
stoichiometry: 1.0
species: 965670

232481
type: SpeciesReference
stoichiometry: 1.0
species: 965690

963846
type: Compartment
constant: true
size: 1.0E-18
spatial dimensions: 3.0

965450
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

967750
type: Reaction
kinetic law: 231147
product: 231135
reactant: 231123
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

231147
type: KineticLaw
local parameters: 509660
local parameters: 509658
notes: kf*DAG-kb*PLCbeta_slash_PC

509660
type: LocalParameter
units: 230126
value: 0.0

509658
type: LocalParameter
units: 230126
value: 1.5E-13

231135
type: SpeciesReference
stoichiometry: 1.0
species: 967090

967090
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: 963881

231123
type: SpeciesReference
stoichiometry: 1.0
species: 964121

971250
type: Reaction
kinetic law: 239594
product: 239582
product: 239570
reactant: 239558
fast: false
reversible: false

239594
type: KineticLaw
local parameters: 510124
notes: k3*AC_slash_CaM_dot_PDE1_slash_CaM_dot_PDE1_slash_CaM_dot_PDE1_cplx

510124
type: LocalParameter
units: 230126
value: 1.0E-11

239582
type: SpeciesReference
stoichiometry: 1.0
species: 966950

239570
type: SpeciesReference
stoichiometry: 1.0
species: 966790

239558
type: SpeciesReference
stoichiometry: 1.0
species: 966970

970470
type: Reaction
kinetic law: 237705
product: 237693
product: 237681
reactant: 237669
fast: false
reversible: false

237705
type: KineticLaw
local parameters: 510041
notes: k3*CaMKII_slash_tot_CaM_CaMKII_slash_CaM_act_286_slash_CaM_act_286_cplx

510041
type: LocalParameter
units: 230126
value: 5.0E-13

237693
type: SpeciesReference
stoichiometry: 1.0
species: 967230

237681
type: SpeciesReference
stoichiometry: 1.0
species: 965750

237669
type: SpeciesReference
stoichiometry: 1.0
species: 965850

969790
type: Reaction
kinetic law: 236036
product: 236024
product: 236012
reactant: 236000
fast: false
reversible: false

236036
type: KineticLaw
local parameters: 509975
notes: k3*MKP_minus_1_slash_MKP1_minus_thr_minus_deph_slash_MKP1_minus_thr_minus_deph_cplx

509975
type: LocalParameter
units: 230126
value: 1.0E-12

236024
type: SpeciesReference
stoichiometry: 1.0
species: 964900

236012
type: SpeciesReference
stoichiometry: 1.0
species: 964720

236000
type: SpeciesReference
stoichiometry: 1.0
species: 964940

970250
type: Reaction
kinetic law: 237148
product: 237136
reactant: 237124
reactant: 237112
fast: false
reversible: true

237148
type: KineticLaw
local parameters: 510023
local parameters: 510021
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

510023
type: LocalParameter
units: 230126
value: 8.0E-14

510021
type: LocalParameter
units: 230211
value: 1.98E-13

237136
type: SpeciesReference
stoichiometry: 1.0
species: 965370

237124
type: SpeciesReference
stoichiometry: 1.0
species: 965350

237112
type: SpeciesReference
stoichiometry: 1.0
species: 965180

970354
type: Reaction
kinetic law: 237389
product: 237377
product: 237365
reactant: 237352
fast: false
reversible: false

237389
type: KineticLaw
local parameters: 510031
notes: k3*EGFR_slash_L_dot_EGFR_slash_phosph_Shc_slash_phosph_Shc_cplx

510031
type: LocalParameter
units: 230126
value: 2.0E-13

237377
type: SpeciesReference
stoichiometry: 1.0
species: 965411

237365
type: SpeciesReference
stoichiometry: 1.0
species: 965490

237352
type: SpeciesReference
stoichiometry: 1.0
species: 965450

968050
type: Reaction
kinetic law: 231875
product: 231862
reactant: 231850
reactant: 231838
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

231875
type: KineticLaw
local parameters: 509720
local parameters: 509718
notes: kf*BetaGamma*Ras_slash_inact_minus_GEF-kb*Ras_slash_GEF_minus_Gprot_minus_bg

509720
type: LocalParameter
units: 230126
value: 1.0E-12

509718
type: LocalParameter
units: 230211
value: 6.0E-12

231862
type: SpeciesReference
stoichiometry: 1.0
species: 965060

231850
type: SpeciesReference
stoichiometry: 1.0
species: 965100

231838
type: SpeciesReference
stoichiometry: 1.0
species: 964540

968410
type: Reaction
kinetic law: 232641
product: 232628
reactant: 232616
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

232641
type: KineticLaw
local parameters: 509792
local parameters: 509790
notes: kf*CaMKII_slash_CaMKII-kb*CaMKII_slash_CaMKII_minus_thr286

509792
type: LocalParameter
units: 230126
value: 0.0

509790
type: LocalParameter
units: 230126
value: 3.0E-15

232628
type: SpeciesReference
stoichiometry: 1.0
species: 965790

232616
type: SpeciesReference
stoichiometry: 1.0
species: 965710

967950
type: Reaction
kinetic law: 231620
product: 231608
reactant: 231596
reactant: 231583
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

231620
type: KineticLaw
local parameters: 509700
local parameters: 509698
notes: kf*Glu*Gq_slash_Rec_minus_Gq-kb*Gq_slash_Rec_minus_Glu_minus_Gq

509700
type: LocalParameter
units: 230126
value: 1.0E-13

509698
type: LocalParameter
units: 230211
value: 1.68E-11

231608
type: SpeciesReference
stoichiometry: 1.0
species: 964620

231596
type: SpeciesReference
stoichiometry: 1.0
species: 964600

231583
type: SpeciesReference
stoichiometry: 1.0
species: 967050

967050
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: 963861

970950
type: Reaction
kinetic law: 238867
product: 238855
product: 238843
reactant: 238831
fast: false
reversible: false

238867
type: KineticLaw
local parameters: 510086
notes: k3*PP2A_slash_PP2A_minus_dephosph_minus_PP1_minus_I_star__slash_PP2A_minus_dephosph_minus_PP1_minus_I_star__cplx

510086
type: LocalParameter
units: 230126
value: 6.0E-12

238855
type: SpeciesReference
stoichiometry: 1.0
species: 966270

238843
type: SpeciesReference
stoichiometry: 1.0
species: 966250

238831
type: SpeciesReference
stoichiometry: 1.0
species: 966310

970170
type: Reaction
kinetic law: 236954
product: 236942
reactant: 236930
reactant: 236918
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

236954
type: KineticLaw
local parameters: 510013
local parameters: 510011
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

510013
type: LocalParameter
units: 230126
value: 3.6E-11

510011
type: LocalParameter
units: 230211
value: 6.0E-12

236942
type: SpeciesReference
stoichiometry: 1.0
species: 965291

965291
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

236930
type: SpeciesReference
stoichiometry: 1.0
species: 965275

236918
type: SpeciesReference
stoichiometry: 1.0
species: 966190

969250
type: Reaction
kinetic law: 234694
product: 234682
reactant: 234670
reactant: 234658
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

234694
type: KineticLaw
local parameters: 509929
local parameters: 509928
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

509929
type: LocalParameter
units: 230126
value: 1.44E-10

509928
type: LocalParameter
units: 230211
value: 9.0E-12

234682
type: SpeciesReference
stoichiometry: 1.0
species: 964360

234670
type: SpeciesReference
stoichiometry: 1.0
species: 964341

234658
type: SpeciesReference
stoichiometry: 1.0
species: 967010

965810
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

969970
type: Reaction
kinetic law: 236470
product: 236458
reactant: 236446
reactant: 236434
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

236470
type: KineticLaw
local parameters: 509992
local parameters: 509991
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

509992
type: LocalParameter
units: 230126
value: 8.0E-14

509991
type: LocalParameter
units: 230211
value: 1.98E-13

236458
type: SpeciesReference
stoichiometry: 1.0
species: 965080

236446
type: SpeciesReference
stoichiometry: 1.0
species: 965060

236434
type: SpeciesReference
stoichiometry: 1.0
species: 965180

968531
type: Reaction
kinetic law: 232967
product: 232955
product: 232943
reactant: 232931
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

232967
type: KineticLaw
local parameters: 509820
local parameters: 509818
notes: kf*PP1_slash_PP1_minus_I1-kb*PP1_minus_active*PP1_slash_I1

509820
type: LocalParameter
units: 230211
value: 0.0

509818
type: LocalParameter
units: 230126
value: 1.0E-12

232955
type: SpeciesReference
stoichiometry: 1.0
species: 966190

232943
type: SpeciesReference
stoichiometry: 1.0
species: 965910

232931
type: SpeciesReference
stoichiometry: 1.0
species: 966250

970190
type: Reaction
kinetic law: 237002
product: 236990
product: 236978
reactant: 236966
fast: false
reversible: false

237002
type: KineticLaw
local parameters: 510015
notes: k3*PKA_minus_active_slash_PKA_minus_phosph_minus_I1_slash_PKA_minus_phosph_minus_I1_cplx

510015
type: LocalParameter
units: 230126
value: 9.0E-12

236990
type: SpeciesReference
stoichiometry: 1.0
species: 965275

236978
type: SpeciesReference
stoichiometry: 1.0
species: 966210

236966
type: SpeciesReference
stoichiometry: 1.0
species: 965291

970530
type: Reaction
kinetic law: 237850
product: 237838
reactant: 237826
reactant: 237814
fast: false
reversible: true

237850
type: KineticLaw
local parameters: 510046
local parameters: 510045
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

510046
type: LocalParameter
units: 230126
value: 2.0E-12

510045
type: LocalParameter
units: 230211
value: 1.4286E-14

237838
type: SpeciesReference
stoichiometry: 1.0
species: 965890

965890
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

237826
type: SpeciesReference
stoichiometry: 1.0
species: 967250

237814
type: SpeciesReference
stoichiometry: 1.0
species: 965730

967730
type: Reaction
kinetic law: 231111
product: 231098
reactant: 231086
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

231111
type: KineticLaw
local parameters: 509656
local parameters: 509654
notes: kf*IP3-kb*PLCbeta_slash_Inositol

509656
type: LocalParameter
units: 230126
value: 0.0

509654
type: LocalParameter
units: 230126
value: 2.5E-12

231098
type: SpeciesReference
stoichiometry: 1.0
species: 967070

231086
type: SpeciesReference
stoichiometry: 1.0
species: 964461

970550
type: Reaction
kinetic law: 237899
product: 237887
product: 237874
reactant: 237862
fast: false
reversible: false

237899
type: KineticLaw
local parameters: 510047
notes: k3*CaMKII_slash_tot_autonomous_CaMKII_slash_auton_286_slash_auton_286_cplx

510047
type: LocalParameter
units: 230126
value: 5.0E-13

237887
type: SpeciesReference
stoichiometry: 1.0
species: 967250

237874
type: SpeciesReference
stoichiometry: 1.0
species: 965750

237862
type: SpeciesReference
stoichiometry: 1.0
species: 965890

971130
type: Reaction
kinetic law: 239303
product: 239291
product: 239279
reactant: 239267
fast: false
reversible: false

239303
type: KineticLaw
local parameters: 510115
notes: k3*AC_slash_cAMP_minus_PDE_slash_PDE_slash_PDE_cplx

510115
type: LocalParameter
units: 230126
value: 1.0E-11

239291
type: SpeciesReference
stoichiometry: 1.0
species: 966830

239279
type: SpeciesReference
stoichiometry: 1.0
species: 966790

239267
type: SpeciesReference
stoichiometry: 1.0
species: 966850

968490
type: Reaction
kinetic law: 232834
product: 232822
reactant: 232810
reactant: 232797
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

232834
type: KineticLaw
local parameters: 509808
local parameters: 509806
notes: kf*CaM_slash_neurogranin*CaM_slash_CaM-kb*CaM_slash_neurogranin_minus_CaM

509808
type: LocalParameter
units: 230126
value: 1.0E-12

509806
type: LocalParameter
units: 230211
value: 3.0E-13

232822
type: SpeciesReference
stoichiometry: 1.0
species: 966030

966030
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

232810
type: SpeciesReference
stoichiometry: 1.0
species: 966010

232797
type: SpeciesReference
stoichiometry: 1.0
species: 966070

967850
type: Reaction
kinetic law: 231389
product: 231377
reactant: 231365
reactant: 231353
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

231389
type: KineticLaw
local parameters: 509680
local parameters: 509678
notes: kf*Gq_slash_mGluR*Glu-kb*Gq_slash_Rec_minus_Glu

509680
type: LocalParameter
units: 230126
value: 1.0E-11

509678
type: LocalParameter
units: 230211
value: 1.68E-11

231377
type: SpeciesReference
stoichiometry: 1.0
species: 964581

231365
type: SpeciesReference
stoichiometry: 1.0
species: 967050

231353
type: SpeciesReference
stoichiometry: 1.0
species: 964580

968510
type: Reaction
kinetic law: 232870
product: 232858
reactant: 232846
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

232870
type: KineticLaw
local parameters: 509812
local parameters: 509810
notes: kf*CaM_slash_neurogranin_star_-kb*CaM_slash_neurogranin

509812
type: LocalParameter
units: 230126
value: 0.0

509810
type: LocalParameter
units: 230126
value: 5.0E-15

232858
type: SpeciesReference
stoichiometry: 1.0
species: 966070

232846
type: SpeciesReference
stoichiometry: 1.0
species: 966050

967470
type: Reaction
kinetic law: 230526
product: 230513
reactant: 230501
notes: Assume slowish too. Schaechter and Benowitz
fast: false
reversible: true

230526
type: KineticLaw
local parameters: 509604
local parameters: 509602
notes: kf*PKC_slash_PKC_minus_DAG_minus_AA-kb*PKC_slash_PKC_minus_DAG_minus_AA_star_

509604
type: LocalParameter
units: 230126
value: 2.0E-13

509602
type: LocalParameter
units: 230126
value: 2.0E-12

230513
type: SpeciesReference
stoichiometry: 1.0
species: 963921

230501
type: SpeciesReference
stoichiometry: 1.0
species: 964081

969110
type: Reaction
kinetic law: 234357
product: 234345
product: 234333
product: 234320
reactant: 234308
fast: false
reversible: false

234357
type: KineticLaw
local parameters: 509918
notes: k3*PKC_minus_active_slash_PKC_minus_phosph_minus_ng_minus_CaM_slash_PKC_minus_phosph_minus_ng_minus_CaM_cplx

509918
type: LocalParameter
units: 230126
value: 3.5E-13

234345
type: SpeciesReference
stoichiometry: 1.0
species: 967210

234333
type: SpeciesReference
stoichiometry: 1.0
species: 966050

234320
type: SpeciesReference
stoichiometry: 1.0
species: 966010

234308
type: SpeciesReference
stoichiometry: 1.0
species: 964241

970310
type: Reaction
kinetic law: 237292
product: 237280
product: 237268
reactant: 237256
fast: false
reversible: false

237292
type: KineticLaw
local parameters: 510028
notes: k3*EGFR_slash_L_dot_EGFR_slash_phosph_PLC_g_slash_phosph_PLC_g_cplx

510028
type: LocalParameter
units: 230126
value: 2.0E-13

237280
type: SpeciesReference
stoichiometry: 1.0
species: 965411

237268
type: SpeciesReference
stoichiometry: 1.0
species: 965690

237256
type: SpeciesReference
stoichiometry: 1.0
species: 965430

969530
type: Reaction
kinetic law: 235388
product: 235375
reactant: 235362
reactant: 235349
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

235388
type: KineticLaw
local parameters: 509953
local parameters: 509952
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

509953
type: LocalParameter
units: 230126
value: 1.92E-10

509952
type: LocalParameter
units: 230211
value: 4.8E-11

235375
type: SpeciesReference
stoichiometry: 1.0
species: 964520

235362
type: SpeciesReference
stoichiometry: 1.0
species: 964501

235349
type: SpeciesReference
stoichiometry: 1.0
species: 967110

967870
type: Reaction
kinetic law: 231438
product: 231426
product: 231413
reactant: 231401
notes: kf = kg1 = 0.01/sec, kb = 0. This is the basal exchange of GTP for GDP.
fast: false
reversible: true

231438
type: KineticLaw
local parameters: 509684
local parameters: 509682
notes: kf*Gq_slash_G_minus_GDP-kb*G_star_GTP*BetaGamma

509684
type: LocalParameter
units: 230211
value: 0.0

509682
type: LocalParameter
units: 230126
value: 1.0E-16

231426
type: SpeciesReference
stoichiometry: 1.0
species: 964540

231413
type: SpeciesReference
stoichiometry: 1.0
species: 964541

231401
type: SpeciesReference
stoichiometry: 1.0
species: 964561

970330
type: Reaction
kinetic law: 237340
product: 237328
reactant: 237316
reactant: 237304
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

237340
type: KineticLaw
local parameters: 510030
local parameters: 510029
notes: k1*EGFR_slash_SHC*EGFR_slash_L_dot_EGFR-k2*EGFR_slash_L_dot_EGFR_slash_phosph_Shc_slash_phosph_Shc_cplx

510030
type: LocalParameter
units: 230126
value: 8.0E-13

510029
type: LocalParameter
units: 230211
value: 1.2E-12

237328
type: SpeciesReference
stoichiometry: 1.0
species: 965450

237316
type: SpeciesReference
stoichiometry: 1.0
species: 965411

237304
type: SpeciesReference
stoichiometry: 1.0
species: 965470

969090
type: Reaction
kinetic law: 234296
product: 234284
reactant: 234272
reactant: 234260
notes: Rates are 60% those of PKC-phosph-neurogranin. See Huang et al ABB 305:2 570-580 1993
fast: false
reversible: true

234296
type: KineticLaw
local parameters: 509917
local parameters: 509916
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

509917
type: LocalParameter
units: 230126
value: 1.4E-12

509916
type: LocalParameter
units: 230211
value: 6.12E-14

234284
type: SpeciesReference
stoichiometry: 1.0
species: 964241

234272
type: SpeciesReference
stoichiometry: 1.0
species: 967210

234260
type: SpeciesReference
stoichiometry: 1.0
species: 966030

970010
type: Reaction
kinetic law: 236567
product: 236555
reactant: 236543
reactant: 236531
notes: Kinetics same as GEF-bg-act-ras
fast: false
reversible: true

236567
type: KineticLaw
local parameters: 509995
local parameters: 509994
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

509995
type: LocalParameter
units: 230126
value: 8.0E-14

509994
type: LocalParameter
units: 230211
value: 1.98E-13

236555
type: SpeciesReference
stoichiometry: 1.0
species: 965140

236543
type: SpeciesReference
stoichiometry: 1.0
species: 965120

236531
type: SpeciesReference
stoichiometry: 1.0
species: 965180

970930
type: Reaction
kinetic law: 238819
product: 238807
reactant: 238795
reactant: 238782
notes: k1 changed from 3.3e-6 to 6.6e-6
fast: false
reversible: true

238819
type: KineticLaw
local parameters: 510085
local parameters: 510084
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

510085
type: LocalParameter
units: 230126
value: 2.5E-11

510084
type: LocalParameter
units: 230211
value: 3.96E-12

238807
type: SpeciesReference
stoichiometry: 1.0
species: 966310

238795
type: SpeciesReference
stoichiometry: 1.0
species: 966270

238782
type: SpeciesReference
stoichiometry: 1.0
species: 966230

969950
type: Reaction
kinetic law: 236421
product: 236409
product: 236397
reactant: 236385
fast: false
reversible: false

509990
type: LocalParameter
units: 230126
value: 6.0E-12

236409
type: SpeciesReference
stoichiometry: 1.0
species: 964960

236397
type: SpeciesReference
stoichiometry: 1.0
species: 964660

236385
type: SpeciesReference
stoichiometry: 1.0
species: 965040

970650
type: Reaction
kinetic law: 238140
product: 238128
reactant: 238116
reactant: 238104
notes: See Cohen et al
fast: false
reversible: true

238140
type: KineticLaw
local parameters: 510059
local parameters: 510057
notes: k1*CaMKII_slash_CaMK_minus_thr306*PP1_minus_active-k2*PP1_minus_active_slash_Deph_minus_thr306_slash_Deph_minus_thr306_cplx

510059
type: LocalParameter
units: 230126
value: 1.4E-12

510057
type: LocalParameter
units: 230211
value: 3.432E-13

238128
type: SpeciesReference
stoichiometry: 1.0
species: 965950

238116
type: SpeciesReference
stoichiometry: 1.0
species: 965910

238104
type: SpeciesReference
stoichiometry: 1.0
species: 965810

967810
type: Reaction
kinetic law: 231293
product: 231281
reactant: 231269
reactant: 231257
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

231293
type: KineticLaw
local parameters: 509672
local parameters: 509670
notes: kf*PLCbeta_slash_PLC*G_star_GTP-kb*PLCbeta_slash_PLC_minus_Gq

509672
type: LocalParameter
units: 230126
value: 1.0E-12

509670
type: LocalParameter
units: 230211
value: 2.52E-12

231281
type: SpeciesReference
stoichiometry: 1.0
species: 964521

231269
type: SpeciesReference
stoichiometry: 1.0
species: 964541

231257
type: SpeciesReference
stoichiometry: 1.0
species: 964480

969310
type: Reaction
kinetic law: 234839
product: 234827
product: 234815
reactant: 234803
fast: false
reversible: false

234839
type: KineticLaw
local parameters: 509936
notes: k3*PLA2_slash_DAG_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx

509936
type: LocalParameter
units: 230126
value: 6.0E-11

234827
type: SpeciesReference
stoichiometry: 1.0
species: 964361

234815
type: SpeciesReference
stoichiometry: 1.0
species: 964141

234803
type: SpeciesReference
stoichiometry: 1.0
species: 964380

968690
type: Reaction
kinetic law: 233357
product: 233344
reactant: 233332
reactant: 233320
fast: false
reversible: true

233357
type: KineticLaw
local parameters: 509852
local parameters: 509850
notes: kf*PKA_slash_R2C2_minus_cAMP2*cAMP-kb*PKA_slash_R2C2_minus_cAMP3

509852
type: LocalParameter
units: 230126
value: 1.1E-10

509850
type: LocalParameter
units: 230211
value: 7.5E-11

233344
type: SpeciesReference
stoichiometry: 1.0
species: 966530

233332
type: SpeciesReference
stoichiometry: 1.0
species: 966650

233320
type: SpeciesReference
stoichiometry: 1.0
species: 966510

970670
type: Reaction
kinetic law: 238188
product: 238176
product: 238164
reactant: 238152
fast: false
reversible: false

238188
type: KineticLaw
local parameters: 510061
notes: k3*PP1_minus_active_slash_Deph_minus_thr306_slash_Deph_minus_thr306_cplx

510061
type: LocalParameter
units: 230126
value: 3.5E-13

238176
type: SpeciesReference
stoichiometry: 1.0
species: 965910

238164
type: SpeciesReference
stoichiometry: 1.0
species: 965710

238152
type: SpeciesReference
stoichiometry: 1.0
species: 965950

967610
type: Reaction
kinetic law: 230857
product: 230844
reactant: 230832
reactant: 230820
fast: false
reversible: true

230857
type: KineticLaw
local parameters: 509632
local parameters: 509630
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star_

509632
type: LocalParameter
units: 230126
value: 1.0E-13

509630
type: LocalParameter
units: 230211
value: 1.2E-14

230844
type: SpeciesReference
stoichiometry: 1.0
species: 964341

230832
type: SpeciesReference
stoichiometry: 1.0
species: 964301

230820
type: SpeciesReference
stoichiometry: 1.0
species: 967030

970710
type: Reaction
kinetic law: 238285
product: 238273
product: 238261
reactant: 238248
fast: false
reversible: false

238285
type: KineticLaw
local parameters: 510066
notes: k3*PP1_minus_active_slash_Deph_minus_thr286c_slash_Deph_minus_thr286c_cplx

510066
type: LocalParameter
units: 230126
value: 3.5E-13

238273
type: SpeciesReference
stoichiometry: 1.0
species: 965910

238261
type: SpeciesReference
stoichiometry: 1.0
species: 965810

238248
type: SpeciesReference
stoichiometry: 1.0
species: 965970

969230
type: Reaction
kinetic law: 234646
product: 234634
product: 234621
reactant: 234609
fast: false
reversible: false

234646
type: KineticLaw
local parameters: 509927
notes: k3*PLA2_slash_PIP2_minus_PLA2_star__slash_kenz_slash_kenz_cplx

509927
type: LocalParameter
units: 230126
value: 1.104E-11

234634
type: SpeciesReference
stoichiometry: 1.0
species: 964321

234621
type: SpeciesReference
stoichiometry: 1.0
species: 964141

234609
type: SpeciesReference
stoichiometry: 1.0
species: 964340

970430
type: Reaction
kinetic law: 237607
product: 237595
product: 237583
reactant: 237570
fast: false
reversible: false

237607
type: KineticLaw
local parameters: 510038
notes: k3*CaMKII_slash_tot_CaM_CaMKII_slash_CaM_act_305_slash_CaM_act_305_cplx

510038
type: LocalParameter
units: 230126
value: 6.0E-12

237595
type: SpeciesReference
stoichiometry: 1.0
species: 967230

237583
type: SpeciesReference
stoichiometry: 1.0
species: 965770

237570
type: SpeciesReference
stoichiometry: 1.0
species: 965830

968170
type: Reaction
kinetic law: 232116
product: 232104
reactant: 232092
reactant: 232080
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

232116
type: KineticLaw
local parameters: 509744
local parameters: 509742
notes: kf*EGFR_slash_EGFR*EGFR_slash_EGF-kb*EGFR_slash_L_dot_EGFR

509744
type: LocalParameter
units: 230126
value: 2.5E-13

509742
type: LocalParameter
units: 230211
value: 4.2E-12

232104
type: SpeciesReference
stoichiometry: 1.0
species: 965411

232092
type: SpeciesReference
stoichiometry: 1.0
species: 967150

967150
type: Species
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861

232080
type: SpeciesReference
stoichiometry: 1.0
species: 965390

965390
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.166666666666667
initial amount: NaN
in compartment: 963861

968930
type: Reaction
kinetic law: 233912
product: 233900
reactant: 233888
reactant: 233876
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
fast: false
reversible: true

233912
type: KineticLaw
local parameters: 509900
local parameters: 509898
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

509900
type: LocalParameter
units: 230126
value: 1.6E-11

509898
type: LocalParameter
units: 230211
value: 3.0E-13

233900
type: SpeciesReference
stoichiometry: 1.0
species: 964161

233888
type: SpeciesReference
stoichiometry: 1.0
species: 967210

233876
type: SpeciesReference
stoichiometry: 1.0
species: 964641

971110
type: Reaction
kinetic law: 239255
product: 239243
reactant: 239231
reactant: 239219
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

239255
type: KineticLaw
local parameters: 510113
local parameters: 510111
notes: k1*cAMP*AC_slash_cAMP_minus_PDE-k2*AC_slash_cAMP_minus_PDE_slash_PDE_slash_PDE_cplx

510113
type: LocalParameter
units: 230126
value: 4.0E-11

510111
type: LocalParameter
units: 230211
value: 2.52E-12

239243
type: SpeciesReference
stoichiometry: 1.0
species: 966850

239231
type: SpeciesReference
stoichiometry: 1.0
species: 966830

239219
type: SpeciesReference
stoichiometry: 1.0
species: 966650

970270
type: Reaction
kinetic law: 237196
product: 237184
product: 237172
reactant: 237160
fast: false
reversible: false

237196
type: KineticLaw
local parameters: 510025
notes: k3*Shc_star__dot_Sos_dot_Grb2_slash_Sos_dot_Ras_GEF_slash_Sos_dot_Ras_GEF_cplx

510025
type: LocalParameter
units: 230126
value: 2.0E-14

237184
type: SpeciesReference
stoichiometry: 1.0
species: 965350

237172
type: SpeciesReference
stoichiometry: 1.0
species: 965160

237160
type: SpeciesReference
stoichiometry: 1.0
species: 965370

968470
type: Reaction
kinetic law: 232785
product: 232773
reactant: 232761
reactant: 232749
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

232785
type: KineticLaw
local parameters: 509804
local parameters: 509802
notes: kf*CaM_minus_Ca3*Ca-kb*CaM_minus_Ca4

509804
type: LocalParameter
units: 230126
value: 1.0E-11

509802
type: LocalParameter
units: 230211
value: 4.65E-13

232773
type: SpeciesReference
stoichiometry: 1.0
species: 965330

232761
type: SpeciesReference
stoichiometry: 1.0
species: 967190

232749
type: SpeciesReference
stoichiometry: 1.0
species: 966090

970450
type: Reaction
kinetic law: 237657
product: 237644
reactant: 237632
reactant: 237620
fast: false
reversible: true

237657
type: KineticLaw
local parameters: 510040
local parameters: 510039
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

510040
type: LocalParameter
units: 230126
value: 2.0E-12

510039
type: LocalParameter
units: 230211
value: 2.20068E-14

237644
type: SpeciesReference
stoichiometry: 1.0
species: 965850

237632
type: SpeciesReference
stoichiometry: 1.0
species: 967230

237620
type: SpeciesReference
stoichiometry: 1.0
species: 965730

969850
type: Reaction
kinetic law: 236180
product: 236168
reactant: 236156
reactant: 236144
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

509983
type: LocalParameter
units: 230126
value: 2.5E-11

509982
type: LocalParameter
units: 230211
value: 1.98E-12

236168
type: SpeciesReference
stoichiometry: 1.0
species: 965000

236156
type: SpeciesReference
stoichiometry: 1.0
species: 964960

236144
type: SpeciesReference
stoichiometry: 1.0
species: 964740

970290
type: Reaction
kinetic law: 237244
product: 237232
reactant: 237220
reactant: 237208
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

237244
type: KineticLaw
local parameters: 510027
local parameters: 510026
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

510027
type: LocalParameter
units: 230126
value: 8.0E-13

510026
type: LocalParameter
units: 230211
value: 3.0E-12

237232
type: SpeciesReference
stoichiometry: 1.0
species: 965430

237220
type: SpeciesReference
stoichiometry: 1.0
species: 965411

237208
type: SpeciesReference
stoichiometry: 1.0
species: 965670

970910
type: Reaction
kinetic law: 238770
product: 238758
product: 238746
reactant: 238734
fast: false
reversible: false

238770
type: KineticLaw
local parameters: 510083
notes: k3*PP2A_slash_PP2A_minus_dephosph_minus_I1_slash_PP2A_minus_dephosph_minus_I1_cplx

510083
type: LocalParameter
units: 230126
value: 6.0E-12

238758
type: SpeciesReference
stoichiometry: 1.0
species: 966270

238746
type: SpeciesReference
stoichiometry: 1.0
species: 966190

238734
type: SpeciesReference
stoichiometry: 1.0
species: 966290

968710
type: Reaction
kinetic law: 233405
product: 233393
reactant: 233381
reactant: 233369
fast: false
reversible: true

233405
type: KineticLaw
local parameters: 509856
local parameters: 509854
notes: kf*cAMP*PKA_slash_R2C2_minus_cAMP3-kb*PKA_slash_R2C2_minus_cAMP4

509856
type: LocalParameter
units: 230126
value: 3.25E-11

509854
type: LocalParameter
units: 230211
value: 7.5E-11

233393
type: SpeciesReference
stoichiometry: 1.0
species: 966550

233381
type: SpeciesReference
stoichiometry: 1.0
species: 966530

233369
type: SpeciesReference
stoichiometry: 1.0
species: 966650

969650
type: Reaction
kinetic law: 235700
product: 235688
reactant: 235675
reactant: 235662
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

235700
type: KineticLaw
local parameters: 509965
local parameters: 509964
notes: k1*MAPK_slash_MAPKK*MAPK_slash_Raf_minus_GTP_minus_Ras_star_-k2*MAPK_slash_Raf_minus_GTP_minus_Ras_star__slash_Raf_minus_GTP_minus_Ras_star__dot_1_slash_Raf_minus_GTP_minus_Ras_star__dot_1_cplx

509965
type: LocalParameter
units: 230126
value: 4.2E-13

509964
type: LocalParameter
units: 230211
value: 3.3E-12

235688
type: SpeciesReference
stoichiometry: 1.0
species: 964860

235675
type: SpeciesReference
stoichiometry: 1.0
species: 964840

235662
type: SpeciesReference
stoichiometry: 1.0
species: 964680

969930
type: Reaction
kinetic law: 236372
product: 236360
reactant: 236348
reactant: 236336
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

509989
type: LocalParameter
units: 230126
value: 2.5E-11

509988
type: LocalParameter
units: 230211
value: 1.98E-12

236360
type: SpeciesReference
stoichiometry: 1.0
species: 965040

236348
type: SpeciesReference
stoichiometry: 1.0
species: 964960

236336
type: SpeciesReference
stoichiometry: 1.0
species: 964701

970150
type: Reaction
kinetic law: 236906
product: 236894
product: 236882
reactant: 236870
fast: false
reversible: false

236906
type: KineticLaw
local parameters: 510010
notes: k3*PKA_minus_active_slash_PKA_minus_phosph_minus_GEF_slash_PKA_minus_phosph_minus_GEF_cplx

510010
type: LocalParameter
units: 230126
value: 9.0E-12

236894
type: SpeciesReference
stoichiometry: 1.0
species: 965275

236882
type: SpeciesReference
stoichiometry: 1.0
species: 965260

236870
type: SpeciesReference
stoichiometry: 1.0
species: 965290

970830
type: Reaction
kinetic law: 238577
product: 238565
product: 238552
reactant: 238539
fast: false
reversible: false

238577
type: KineticLaw
local parameters: 510077
notes: k3*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_inhib1_slash_dephosph_inhib1_cplx

510077
type: LocalParameter
units: 230126
value: 3.4E-13

238565
type: SpeciesReference
stoichiometry: 1.0
species: 967270

238552
type: SpeciesReference
stoichiometry: 1.0
species: 966190

238539
type: SpeciesReference
stoichiometry: 1.0
species: 966150

969190
type: Reaction
kinetic law: 234549
product: 234537
product: 234525
reactant: 234513
fast: false
reversible: false

234549
type: KineticLaw
local parameters: 509924
notes: k3*PLA2_slash_PLA2_minus_Ca_star__slash_kenz_slash_kenz_cplx

509924
type: LocalParameter
units: 230126
value: 5.4E-12

234537
type: SpeciesReference
stoichiometry: 1.0
species: 964301

234525
type: SpeciesReference
stoichiometry: 1.0
species: 964141

234513
type: SpeciesReference
stoichiometry: 1.0
species: 964320

970110
type: Reaction
kinetic law: 236808
product: 236796
product: 236784
reactant: 236771
fast: false
reversible: false

236808
type: KineticLaw
local parameters: 510005
notes: k3*Ras_slash_CaM_minus_GEF_slash_CaM_minus_GEF_minus_act_minus_ras_slash_CaM_minus_GEF_minus_act_minus_ras_cplx

510005
type: LocalParameter
units: 230126
value: 2.0E-14

236796
type: SpeciesReference
stoichiometry: 1.0
species: 965263

236784
type: SpeciesReference
stoichiometry: 1.0
species: 965160

236771
type: SpeciesReference
stoichiometry: 1.0
species: 965272

970510
type: Reaction
kinetic law: 237802
product: 237790
product: 237778
reactant: 237766
fast: false
reversible: false

237802
type: KineticLaw
local parameters: 510044
notes: k3*CaMKII_slash_tot_autonomous_CaMKII_slash_auton_305_slash_auton_305_cplx

510044
type: LocalParameter
units: 230126
value: 6.0E-12

237790
type: SpeciesReference
stoichiometry: 1.0
species: 967250

237778
type: SpeciesReference
stoichiometry: 1.0
species: 965770

237766
type: SpeciesReference
stoichiometry: 1.0
species: 965870

971010
type: Reaction
kinetic law: 239012
modifier: 239000
product: 238988
reactant: 238976
fast: false
reversible: false

239012
type: KineticLaw
local parameters: 510093
local parameters: 510091
notes: kcat*AC_slash_AC1_minus_CaM*AC_slash_ATP/(Km+AC_slash_ATP)

510093
type: LocalParameter
units: 230090
value: 20.0

510091
type: LocalParameter
units: 230126
value: 1.8E-11

238988
type: SpeciesReference
stoichiometry: 1.0
species: 966650

238976
type: SpeciesReference
stoichiometry: 1.0
species: 967170

969430
type: Reaction
kinetic law: 235129
product: 235117
product: 235105
reactant: 235093
fast: false
reversible: false

235129
type: KineticLaw
local parameters: 509945
notes: k3*MAPK_star__slash_MAPK_star__minus_feedback_slash_MAPK_star__minus_feedback_cplx

509945
type: LocalParameter
units: 230126
value: 1.0E-11

235117
type: SpeciesReference
stoichiometry: 1.0
species: 964421

235105
type: SpeciesReference
stoichiometry: 1.0
species: 964701

235093
type: SpeciesReference
stoichiometry: 1.0
species: 964441

967390
type: Reaction
kinetic law: 230368
product: 230356
reactant: 230344
reactant: 230332
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

230368
type: KineticLaw
local parameters: 509593
local parameters: 509592
notes: kf*DAG*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_DAG

509593
type: LocalParameter
units: 230126
value: 8.6348E-12

509592
type: LocalParameter
units: 230211
value: 7.9998E-15

230356
type: SpeciesReference
stoichiometry: 1.0
species: 964041

230344
type: SpeciesReference
stoichiometry: 1.0
species: 963901

230332
type: SpeciesReference
stoichiometry: 1.0
species: 964121

971070
type: Reaction
kinetic law: 239158
modifier: 239146
product: 239134
reactant: 239122
fast: false
reversible: false

239158
type: KineticLaw
local parameters: 510105
local parameters: 510103
notes: kcat*AC_slash_AC1_minus_Gs*AC_slash_ATP/(Km+AC_slash_ATP)

510105
type: LocalParameter
units: 230090
value: 20.0

510103
type: LocalParameter
units: 230126
value: 1.8E-11

239134
type: SpeciesReference
stoichiometry: 1.0
species: 966650

239122
type: SpeciesReference
stoichiometry: 1.0
species: 967170

969710
type: Reaction
kinetic law: 235844
product: 235832
product: 235820
reactant: 235808
fast: false
reversible: false

235844
type: KineticLaw
local parameters: 509969
notes: k3*MAPK_slash_Raf_minus_GTP_minus_Ras_star__slash_Raf_minus_GTP_minus_Ras_star__dot_2_slash_Raf_minus_GTP_minus_Ras_star__dot_2_cplx

509969
type: LocalParameter
units: 230126
value: 1.05E-13

235832
type: SpeciesReference
stoichiometry: 1.0
species: 964840

235820
type: SpeciesReference
stoichiometry: 1.0
species: 964740

235808
type: SpeciesReference
stoichiometry: 1.0
species: 964880

968910
type: Reaction
kinetic law: 233864
product: 233852
reactant: 233840
reactant: 233828
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

233864
type: KineticLaw
local parameters: 509896
local parameters: 509894
notes: kf*AC_slash_PDE1*CaM_minus_Ca4-kb*AC_slash_CaM_dot_PDE1

509896
type: LocalParameter
units: 230126
value: 5.0E-12

509894
type: LocalParameter
units: 230211
value: 7.2E-10

233852
type: SpeciesReference
stoichiometry: 1.0
species: 966950

233840
type: SpeciesReference
stoichiometry: 1.0
species: 965330

233828
type: SpeciesReference
stoichiometry: 1.0
species: 966910

968650
type: Reaction
kinetic law: 233259
product: 233247
reactant: 233235
reactant: 233223
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

233259
type: KineticLaw
local parameters: 509844
local parameters: 509842
notes: kf*PKA_slash_R2C2*cAMP-kb*PKA_slash_R2C2_minus_cAMP

509844
type: LocalParameter
units: 230126
value: 3.3E-11

509842
type: LocalParameter
units: 230211
value: 5.4E-11

233247
type: SpeciesReference
stoichiometry: 1.0
species: 966490

233235
type: SpeciesReference
stoichiometry: 1.0
species: 966650

233223
type: SpeciesReference
stoichiometry: 1.0
species: 966470

969510
type: Reaction
kinetic law: 235336
product: 235324
product: 235312
product: 235300
reactant: 235288
fast: false
reversible: false

235336
type: KineticLaw
local parameters: 509951
notes: k3*PLCbeta_slash_PLC_minus_Ca_slash_PLC_minus_Ca_slash_PLC_minus_Ca_cplx

509951
type: LocalParameter
units: 230126
value: 1.0E-11

235324
type: SpeciesReference
stoichiometry: 1.0
species: 964481

235312
type: SpeciesReference
stoichiometry: 1.0
species: 964461

235300
type: SpeciesReference
stoichiometry: 1.0
species: 964121

235288
type: SpeciesReference
stoichiometry: 1.0
species: 964500

969050
type: Reaction
kinetic law: 234200
product: 234188
reactant: 234176
reactant: 234164
notes: Rates from Huang et al ABB 305:2 570-580 1993
fast: false
reversible: true

234200
type: KineticLaw
local parameters: 509914
local parameters: 509913
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

509914
type: LocalParameter
units: 230126
value: 2.34E-12

509913
type: LocalParameter
units: 230211
value: 1.02E-13

234188
type: SpeciesReference
stoichiometry: 1.0
species: 964221

234176
type: SpeciesReference
stoichiometry: 1.0
species: 967210

234164
type: SpeciesReference
stoichiometry: 1.0
species: 966070

968990
type: Reaction
kinetic law: 234056
product: 234044
product: 234032
reactant: 234020
fast: false
reversible: false

234056
type: KineticLaw
local parameters: 509907
notes: k3*PKC_minus_active_slash_PKC_minus_inact_minus_GAP_slash_PKC_minus_inact_minus_GAP_cplx

509907
type: LocalParameter
units: 230126
value: 4.0E-12

234044
type: SpeciesReference
stoichiometry: 1.0
species: 967210

234032
type: SpeciesReference
stoichiometry: 1.0
species: 965200

234020
type: SpeciesReference
stoichiometry: 1.0
species: 964181