MODEL9089914876
type: SBMLModel
species: 439794
species: 443314
reaction: 444893
reaction: 447073
compartment: 439494
reaction: 446813
reaction: 445034
species: 441214
reaction: 446533
species: 442994
reaction: 447093
species: 443054
species: 443194
species: 442694
reaction: 447133
reaction: 444453
species: 440614
species: 442874
species: 441354
reaction: 446713
species: 442014
reaction: 445613
species: 441094
reaction: 445573
reaction: 445073
species: 442774
reaction: 445113
reaction: 446933
compartment: 439514
reaction: 445513
species: 441814
species: 442054
reaction: 444053
species: 440554
reaction: 445533
reaction: 445313
species: 441554
species: 440034
species: 441734
species: 439994
reaction: 444073
species: 440194
species: 440374
reaction: 443474
species: 442234
reaction: 445833
reaction: 447213
reaction: 445793
reaction: 445293
reaction: 445333
species: 442914
units def: 462030
species: 439594
species: 440854
reaction: 444173
species: 443114
reaction: 444273
species: 439634
reaction: 444193
species: 441774
species: 443034
reaction: 443594
reaction: 446913
reaction: 444293
reaction: 443694
species: 441014
reaction: 443813
species: 439694
species: 441674
units def: 462115
reaction: 443913
species: 443214
species: 441754
species: 442834
species: 441294
species: 440894
reaction: 444393
species: 442134
species: 442554

439794
type: Species
constant: false
boundary condition: false
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initial concentration: 0.0
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439494
type: Compartment
constant: true
size: 1.5E-15
spatial dimensions: 3.0

443314
type: Species
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

444893
type: Reaction
kinetic law: 465935
product: 465923
product: 465910
reactant: 465898
fast: false
reversible: false

465935
type: KineticLaw
local parameters: 352979
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_raf_slash_PKC_minus_act_minus_raf_cplx

352979
type: LocalParameter
units: 462030
value: 6.0E-15

462055
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND

462043
type: SBMLUnit
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE

465923
type: SpeciesReference
stoichiometry: 1.0
species: 443294

443294
type: Species
constant: false
boundary condition: true
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initial concentration: 0.0
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465910
type: SpeciesReference
stoichiometry: 1.0
species: 440574

440574
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

465898
type: SpeciesReference
stoichiometry: 1.0
species: 439794

447073
type: Reaction
kinetic law: 471288
modifier: 471276
product: 471264
reactant: 471252
fast: false
reversible: false

471288
type: KineticLaw
local parameters: 353303
local parameters: 353300
notes: kcat*AC_slash_AC2_minus_Gs*AC_slash_ATP/(Km+AC_slash_ATP)

353303
type: LocalParameter
units: 461994
value: 20.0

462018
type: SBMLUnit
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE

462006
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE

353300
type: LocalParameter
units: 462030
value: 2.7E-14

442794
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

471264
type: SpeciesReference
stoichiometry: 1.0
species: 442714

442714
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

471252
type: SpeciesReference
stoichiometry: 1.0
species: 443274

443274
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: 439494

446813
type: Reaction
kinetic law: 470655
product: 470643
product: 470631
reactant: 470619
fast: false
reversible: false

470655
type: KineticLaw
local parameters: 353240
notes: k3*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_neurogranin_slash_dephosph_neurogranin_cplx

353240
type: LocalParameter
units: 462030
value: 1.005E-15

470643
type: SpeciesReference
stoichiometry: 1.0
species: 443354

443354
type: Species
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

470631
type: SpeciesReference
stoichiometry: 1.0
species: 442134

442134
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 10.0
initial amount: NaN
in compartment: 439494

470619
type: SpeciesReference
stoichiometry: 1.0
species: 442194

442194
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

445034
type: Reaction
kinetic law: 466271
product: 466259
reactant: 466247
reactant: 466235
notes: Rates are 60% those of PKC-phosph-neurogranin. See Huang et al ABB 305:2 570-580 1993
fast: false
reversible: true

466271
type: KineticLaw
local parameters: 352993
local parameters: 352992
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

352993
type: LocalParameter
units: 462030
value: 2.1E-15

352992
type: LocalParameter
units: 462115
value: 9.18E-17

462152
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND

462140
type: SBMLUnit
exponent: -1.0
scale: -6
multipler: 1.0
kind: MOLE

462128
type: SBMLUnit
exponent: 2.0
scale: 0
multipler: 1.0
kind: LITRE

466259
type: SpeciesReference
stoichiometry: 1.0
species: 439874

439874
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

466247
type: SpeciesReference
stoichiometry: 1.0
species: 443294

466235
type: SpeciesReference
stoichiometry: 1.0
species: 442094

442094
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

441214
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

446533
type: Reaction
kinetic law: 469974
product: 469962
product: 469950
reactant: 469938
fast: false
reversible: false

469974
type: KineticLaw
local parameters: 353177
notes: k3*CaMKII_slash_tot_autonomous_CaMKII_slash_auton_305_slash_auton_305_cplx

353177
type: LocalParameter
units: 462030
value: 9.0E-15

469962
type: SpeciesReference
stoichiometry: 1.0
species: 443334

443334
type: Species
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

469950
type: SpeciesReference
stoichiometry: 1.0
species: 441814

441814
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

469938
type: SpeciesReference
stoichiometry: 1.0
species: 441914

441914
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

442994
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

447093
type: Reaction
kinetic law: 471337
modifier: 471325
product: 471312
reactant: 471300
fast: false
reversible: false

471337
type: KineticLaw
local parameters: 353309
local parameters: 353306
notes: kcat*AC_slash_AC1_minus_Gs*AC_slash_ATP/(Km+AC_slash_ATP)

353309
type: LocalParameter
units: 461994
value: 20.0

353306
type: LocalParameter
units: 462030
value: 2.7E-14

442834
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

471312
type: SpeciesReference
stoichiometry: 1.0
species: 442714

471300
type: SpeciesReference
stoichiometry: 1.0
species: 443274

443054
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

443194
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: 439514

439514
type: Compartment
constant: true
size: 2.5E-21
spatial dimensions: 3.0

442694
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

447133
type: Reaction
kinetic law: 471433
product: 471421
reactant: 471409
reactant: 471397
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

471433
type: KineticLaw
local parameters: 353321
local parameters: 353318
notes: k1*cAMP*AC_slash_cAMP_minus_PDE-k2*AC_slash_cAMP_minus_PDE_slash_PDE_slash_PDE_cplx

353321
type: LocalParameter
units: 462030
value: 6.0E-14

353318
type: LocalParameter
units: 462115
value: 3.78E-15

471421
type: SpeciesReference
stoichiometry: 1.0
species: 442914

442914
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

471409
type: SpeciesReference
stoichiometry: 1.0
species: 442894

442894
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.45
initial amount: NaN
in compartment: 439494

471397
type: SpeciesReference
stoichiometry: 1.0
species: 442714

444453
type: Reaction
kinetic law: 464909
product: 464897
reactant: 464885
reactant: 464873
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

464909
type: KineticLaw
local parameters: 352924
local parameters: 352923
notes: kf*Ca^2*PP2B_slash_CaNAB_minus_Ca2-kb*CaNAB_minus_Ca4

352924
type: LocalParameter
units: 462030
value: 1.5E-15

352923
type: LocalParameter
units: 462067
value: 5.399946E-15

462103
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND

462091
type: SBMLUnit
exponent: -2.0
scale: -6
multipler: 1.0
kind: MOLE

462079
type: SBMLUnit
exponent: 3.0
scale: 0
multipler: 1.0
kind: LITRE

464897
type: SpeciesReference
stoichiometry: 1.0
species: 442394

442394
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

464885
type: SpeciesReference
stoichiometry: 1.0
species: 442454

442454
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

464873
type: SpeciesReference
stoichiometry: 2.0
species: 443074

443074
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.08
initial amount: NaN
in compartment: 439494

440614
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.6
initial amount: NaN
in compartment: 439494

442874
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

441354
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

446713
type: Reaction
kinetic law: 470411
product: 470399
reactant: 470387
reactant: 470375
fast: false
reversible: true

470411
type: KineticLaw
local parameters: 353219
local parameters: 353216
notes: k1*CaMKII_slash_CaMKII_star__star__star_*PP1_minus_active-k2*PP1_minus_active_slash_Deph_minus_thr286c_slash_Deph_minus_thr286c_cplx

353219
type: LocalParameter
units: 462030
value: 2.1E-15

353216
type: LocalParameter
units: 462115
value: 5.147955E-16

470399
type: SpeciesReference
stoichiometry: 1.0
species: 442034

442034
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

470387
type: SpeciesReference
stoichiometry: 1.0
species: 441954

441954
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.8
initial amount: NaN
in compartment: 439494

470375
type: SpeciesReference
stoichiometry: 1.0
species: 441814

442014
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

445613
type: Reaction
kinetic law: 467724
product: 467712
product: 467700
reactant: 467688
fast: false
reversible: false

467724
type: KineticLaw
local parameters: 353051
notes: k3*MAPK_slash_Raf_minus_GTP_minus_Ras_slash_Raf_minus_GTP_minus_Ras_dot_1_slash_Raf_minus_GTP_minus_Ras_dot_1_cplx

353051
type: LocalParameter
units: 462030
value: 4.5E-16

467712
type: SpeciesReference
stoichiometry: 1.0
species: 440754

440754
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

467700
type: SpeciesReference
stoichiometry: 1.0
species: 440734

440734
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

467688
type: SpeciesReference
stoichiometry: 1.0
species: 440774

440774
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

441094
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

445573
type: Reaction
kinetic law: 467626
product: 467614
product: 467602
reactant: 467590
fast: false
reversible: false

467626
type: KineticLaw
local parameters: 353045
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx

353045
type: LocalParameter
units: 462030
value: 4.5E-16

467614
type: SpeciesReference
stoichiometry: 1.0
species: 440674

440674
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

467602
type: SpeciesReference
stoichiometry: 1.0
species: 440154

440154
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

467590
type: SpeciesReference
stoichiometry: 1.0
species: 440714

440714
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

445073
type: Reaction
kinetic law: 466380
product: 466368
reactant: 466356
reactant: 466343
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

466380
type: KineticLaw
local parameters: 352996
local parameters: 352995
notes: k1*AC_slash_AC2*PKC_minus_active-k2*PKC_minus_active_slash_phosph_minus_AC2_slash_phosph_minus_AC2_cplx

352996
type: LocalParameter
units: 462030
value: 2.4E-14

352995
type: LocalParameter
units: 462115
value: 9.000045E-16

466368
type: SpeciesReference
stoichiometry: 1.0
species: 439894

439894
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

466356
type: SpeciesReference
stoichiometry: 1.0
species: 443294

466343
type: SpeciesReference
stoichiometry: 1.0
species: 442814

442814
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.015
initial amount: NaN
in compartment: 439494

442774
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

445113
type: Reaction
kinetic law: 466478
product: 466465
reactant: 466453
reactant: 466441
notes: 10 x raise oct22 12 x oct 24, set k2 = 4 * k3
fast: false
reversible: true

466478
type: KineticLaw
local parameters: 353002
local parameters: 352999
notes: k1*PLA2_slash_APC*PLA2_slash_PLA2_minus_Ca_star_-k2*PLA2_slash_PLA2_minus_Ca_star__slash_kenz_slash_kenz_cplx

353002
type: LocalParameter
units: 462030
value: 3.24E-14

352999
type: LocalParameter
units: 462115
value: 2.025E-15

466465
type: SpeciesReference
stoichiometry: 1.0
species: 439954

439954
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

466453
type: SpeciesReference
stoichiometry: 1.0
species: 439934

439934
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

466441
type: SpeciesReference
stoichiometry: 1.0
species: 443114

443114
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: 439494

446933
type: Reaction
kinetic law: 470945
product: 470933
product: 470921
reactant: 470909
fast: false
reversible: false

470945
type: KineticLaw
local parameters: 353267
notes: k3*PP2A_slash_PP2A_minus_dephosph_minus_I1_slash_PP2A_minus_dephosph_minus_I1_cplx

353267
type: LocalParameter
units: 462030
value: 9.0E-15

470933
type: SpeciesReference
stoichiometry: 1.0
species: 442334

442334
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.12
initial amount: NaN
in compartment: 439494

470921
type: SpeciesReference
stoichiometry: 1.0
species: 442254

442254
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.8
initial amount: NaN
in compartment: 439494

470909
type: SpeciesReference
stoichiometry: 1.0
species: 442354

442354
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

445513
type: Reaction
kinetic law: 467482
product: 467470
reactant: 467458
reactant: 467446
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

467482
type: KineticLaw
local parameters: 353041
local parameters: 353040
notes: k1*MAPK_slash_MAPK*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx

353041
type: LocalParameter
units: 462030
value: 1.8E-15

353040
type: LocalParameter
units: 462115
value: 4.86E-14

467470
type: SpeciesReference
stoichiometry: 1.0
species: 440694

440694
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

467458
type: SpeciesReference
stoichiometry: 1.0
species: 440674

467446
type: SpeciesReference
stoichiometry: 1.0
species: 440614

442054
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

444053
type: Reaction
kinetic law: 464015
product: 464003
reactant: 463991
reactant: 463979
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

464015
type: KineticLaw
local parameters: 352868
local parameters: 352867
notes: kf*EGFR_slash_EGFR*EGFR_slash_EGF-kb*EGFR_slash_L_dot_EGFR

352868
type: LocalParameter
units: 462030
value: 3.75E-16

352867
type: LocalParameter
units: 462115
value: 6.300045E-15

464003
type: SpeciesReference
stoichiometry: 1.0
species: 441454

441454
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

463991
type: SpeciesReference
stoichiometry: 1.0
species: 443254

443254
type: Species
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

463979
type: SpeciesReference
stoichiometry: 1.0
species: 441434

441434
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.166666666666667
initial amount: NaN
in compartment: 439494

440554
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 439494

445533
type: Reaction
kinetic law: 467530
product: 467518
product: 467506
reactant: 467494
fast: false
reversible: false

467530
type: KineticLaw
local parameters: 353042
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx

353042
type: LocalParameter
units: 462030
value: 4.5E-16

467518
type: SpeciesReference
stoichiometry: 1.0
species: 440674

467506
type: SpeciesReference
stoichiometry: 1.0
species: 440654

440654
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

467494
type: SpeciesReference
stoichiometry: 1.0
species: 440694

445313
type: Reaction
kinetic law: 466960
product: 466948
reactant: 466936
reactant: 466924
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

466960
type: KineticLaw
local parameters: 353020
local parameters: 353019
notes: k1*PLA2_slash_PLA2_minus_cytosolic*MAPK_star_-k2*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx

353020
type: LocalParameter
units: 462030
value: 6.0E-14

353019
type: LocalParameter
units: 462115
value: 2.925045E-15

466948
type: SpeciesReference
stoichiometry: 1.0
species: 440174

440174
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

466936
type: SpeciesReference
stoichiometry: 1.0
species: 440154

466924
type: SpeciesReference
stoichiometry: 1.0
species: 439914

439914
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.4
initial amount: NaN
in compartment: 439494

441554
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

440034
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

441734
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

439994
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

444073
type: Reaction
kinetic law: 464051
product: 464039
reactant: 464027
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

464051
type: KineticLaw
local parameters: 352872
local parameters: 352869
notes: kf*EGFR_slash_SHC_star_-kb*EGFR_slash_SHC

352872
type: LocalParameter
units: 462030
value: 0.0

352869
type: LocalParameter
units: 462030
value: 2.50005E-18

464039
type: SpeciesReference
stoichiometry: 1.0
species: 441514

441514
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 439494

464027
type: SpeciesReference
stoichiometry: 1.0
species: 441534

441534
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

440194
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

440374
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

443474
type: Reaction
kinetic law: 462274
product: 462261
reactant: 462248
reactant: 462236
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

462274
type: KineticLaw
local parameters: 352756
local parameters: 352755
notes: kf*DAG*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_DAG

352756
type: LocalParameter
units: 462030
value: 1.29522E-14

352755
type: LocalParameter
units: 462115
value: 1.1999745E-17

462261
type: SpeciesReference
stoichiometry: 1.0
species: 439674

439674
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 8.46311111111111E-23
initial amount: NaN
in compartment: 439494

462248
type: SpeciesReference
stoichiometry: 1.0
species: 439534

439534
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.72077777777778E-17
initial amount: NaN
in compartment: 439494

462236
type: SpeciesReference
stoichiometry: 1.0
species: 439754

439754
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

442234
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

445833
type: Reaction
kinetic law: 468256
product: 468244
reactant: 468232
reactant: 468220
notes: See parent PPhosphatase2A for parms
fast: false
reversible: true

353074
type: LocalParameter
units: 462030
value: 3.6E-14

353071
type: LocalParameter
units: 462115
value: 2.87415E-15

468244
type: SpeciesReference
stoichiometry: 1.0
species: 440954

440954
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

468232
type: SpeciesReference
stoichiometry: 1.0
species: 440934

440934
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 439494

468220
type: SpeciesReference
stoichiometry: 1.0
species: 440574

447213
type: Reaction
kinetic law: 471625
product: 471613
reactant: 471601
reactant: 471589
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

471625
type: KineticLaw
local parameters: 353339
local parameters: 353336
notes: k1*cAMP*AC_slash_PDE1-k2*AC_slash_PDE1_slash_PDE1_slash_PDE1_cplx

353339
type: LocalParameter
units: 462030
value: 1.0005E-14

353336
type: LocalParameter
units: 462115
value: 3.149955E-16

471613
type: SpeciesReference
stoichiometry: 1.0
species: 442994

471601
type: SpeciesReference
stoichiometry: 1.0
species: 442974

442974
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 2.0
initial amount: NaN
in compartment: 439494

471589
type: SpeciesReference
stoichiometry: 1.0
species: 442714

445793
type: Reaction
kinetic law: 468160
product: 468148
reactant: 468135
reactant: 468123
notes: See MKP1-tyr-deph
fast: false
reversible: true

468160
type: KineticLaw
local parameters: 353068
local parameters: 353067
notes: k1*MAPK_star_*MKP_minus_1-k2*MKP_minus_1_slash_MKP1_minus_thr_minus_deph_slash_MKP1_minus_thr_minus_deph_cplx

353068
type: LocalParameter
units: 462030
value: 2.4E-14

353067
type: LocalParameter
units: 462115
value: 2.250045E-13

468148
type: SpeciesReference
stoichiometry: 1.0
species: 440914

440914
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

468135
type: SpeciesReference
stoichiometry: 1.0
species: 440874

440874
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.024
initial amount: NaN
in compartment: 439494

468123
type: SpeciesReference
stoichiometry: 1.0
species: 440154

445293
type: Reaction
kinetic law: 466912
product: 466900
product: 466888
reactant: 466876
fast: false
reversible: false

466912
type: KineticLaw
local parameters: 353018
notes: k3*PLA2_slash_PLA2_star__minus_Ca_slash_kenz_slash_kenz_cplx

353018
type: LocalParameter
units: 462030
value: 1.8E-13

466900
type: SpeciesReference
stoichiometry: 1.0
species: 440094

440094
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

466888
type: SpeciesReference
stoichiometry: 1.0
species: 439774

439774
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

466876
type: SpeciesReference
stoichiometry: 1.0
species: 440114

440114
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

445333
type: Reaction
kinetic law: 467009
product: 466997
product: 466985
reactant: 466972
fast: false
reversible: false

467009
type: KineticLaw
local parameters: 353021
notes: k3*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx

353021
type: LocalParameter
units: 462030
value: 1.5E-14

466997
type: SpeciesReference
stoichiometry: 1.0
species: 440154

466985
type: SpeciesReference
stoichiometry: 1.0
species: 440134

440134
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

466972
type: SpeciesReference
stoichiometry: 1.0
species: 440174

439594
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.38955555555556E-17
initial amount: NaN
in compartment: 439494

440854
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

444173
type: Reaction
kinetic law: 464267
product: 464255
reactant: 464243
reactant: 464231
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

464267
type: KineticLaw
local parameters: 352884
local parameters: 352883
notes: kf*Sos_slash_Grb2*Sos_slash_Sos-kb*Sos_slash_Sos_dot_Grb2

352884
type: LocalParameter
units: 462030
value: 2.52E-17

352883
type: LocalParameter
units: 462115
value: 3.75003E-17

464255
type: SpeciesReference
stoichiometry: 1.0
species: 441614

441614
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

464243
type: SpeciesReference
stoichiometry: 1.0
species: 441654

441654
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.1
initial amount: NaN
in compartment: 439494

464231
type: SpeciesReference
stoichiometry: 1.0
species: 441594

441594
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 439494

444273
type: Reaction
kinetic law: 464498
product: 464486
reactant: 464473
reactant: 464460
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

464498
type: KineticLaw
local parameters: 352898
local parameters: 352897
notes: kf*CaMKII_slash_CaMKII_minus_thr286*CaM_minus_Ca4-kb*CaMKII_slash_CaMKII_minus_thr286_star__minus_CaM

352898
type: LocalParameter
units: 462030
value: 1.5E-16

352897
type: LocalParameter
units: 462115
value: 1.500255E-12

464486
type: SpeciesReference
stoichiometry: 1.0
species: 441794

441794
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

464473
type: SpeciesReference
stoichiometry: 1.0
species: 441374

441374
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

464460
type: SpeciesReference
stoichiometry: 1.0
species: 441834

441834
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

439634
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

444193
type: Reaction
kinetic law: 464315
product: 464303
reactant: 464291
reactant: 464279
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

464315
type: KineticLaw
local parameters: 352888
local parameters: 352885
notes: kf*PLC_g_slash_PLC_g*Ca-kb*PLC_g_slash_Ca_dot_PLC_g

352888
type: LocalParameter
units: 462030
value: 1.5E-14

352885
type: LocalParameter
units: 462115
value: 2.7E-13

464303
type: SpeciesReference
stoichiometry: 1.0
species: 441714

441714
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

464291
type: SpeciesReference
stoichiometry: 1.0
species: 443074

464279
type: SpeciesReference
stoichiometry: 1.0
species: 441674

441674
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.82
initial amount: NaN
in compartment: 439494

441774
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

443034
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

443594
type: Reaction
kinetic law: 462518
product: 462506
reactant: 462494
reactant: 462482
notes: Raise kf from 1.667e-10 to 2e-10 to get better match to data.
fast: false
reversible: true

462518
type: KineticLaw
local parameters: 352772
local parameters: 352771
notes: kf*AA*PKC_slash_PKC_minus_cytosolic-kb*PKC_slash_PKC_minus_AA_star_

352772
type: LocalParameter
units: 462030
value: 1.5E-16

352771
type: LocalParameter
units: 462115
value: 1.799955E-19

462506
type: SpeciesReference
stoichiometry: 1.0
species: 439654

439654
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.81333333333333E-17
initial amount: NaN
in compartment: 439494

462494
type: SpeciesReference
stoichiometry: 1.0
species: 439734

439734
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 439494

462482
type: SpeciesReference
stoichiometry: 1.0
species: 439774

446913
type: Reaction
kinetic law: 470897
product: 470885
reactant: 470873
reactant: 470861
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

470897
type: KineticLaw
local parameters: 353264
local parameters: 353261
notes: k1*PP1_slash_I1_star_*PP2A-k2*PP2A_slash_PP2A_minus_dephosph_minus_I1_slash_PP2A_minus_dephosph_minus_I1_cplx

353264
type: LocalParameter
units: 462030
value: 3.75E-14

353261
type: LocalParameter
units: 462115
value: 5.94E-15

470885
type: SpeciesReference
stoichiometry: 1.0
species: 442354

470873
type: SpeciesReference
stoichiometry: 1.0
species: 442334

470861
type: SpeciesReference
stoichiometry: 1.0
species: 442274

442274
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.001
initial amount: NaN
in compartment: 439494

444293
type: Reaction
kinetic law: 464535
product: 464522
reactant: 464510
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

464535
type: KineticLaw
local parameters: 352902
local parameters: 352899
notes: kf*CaMKII_slash_CaMKII-kb*CaMKII_slash_CaMKII_minus_thr286

352902
type: LocalParameter
units: 462030
value: 0.0

352899
type: LocalParameter
units: 462030
value: 4.5E-18

464522
type: SpeciesReference
stoichiometry: 1.0
species: 441834

464510
type: SpeciesReference
stoichiometry: 1.0
species: 441754

441754
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 70.0
initial amount: NaN
in compartment: 439494

443694
type: Reaction
kinetic law: 462809
product: 462797
reactant: 462785
reactant: 462773
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

462809
type: KineticLaw
local parameters: 352790
local parameters: 352787
notes: kf*DAG*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_DAG_minus_Ca_minus_PLA2_star_

352790
type: LocalParameter
units: 462030
value: 6.0E-15

352787
type: LocalParameter
units: 462115
value: 4.499955E-18

462797
type: SpeciesReference
stoichiometry: 1.0
species: 440054

440054
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

462785
type: SpeciesReference
stoichiometry: 1.0
species: 439934

462773
type: SpeciesReference
stoichiometry: 1.0
species: 439754

441014
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

443813
type: Reaction
kinetic law: 463242
product: 463230
reactant: 463218
reactant: 463206
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

463242
type: KineticLaw
local parameters: 352818
local parameters: 352817
notes: kf*Ca*PLCbeta_slash_PLC_minus_Gq-kb*PLCbeta_slash_PLC_minus_Ca_minus_Gq

352818
type: LocalParameter
units: 462030
value: 1.5E-15

352817
type: LocalParameter
units: 462115
value: 4.499955E-14

463230
type: SpeciesReference
stoichiometry: 1.0
species: 440314

440314
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

463218
type: SpeciesReference
stoichiometry: 1.0
species: 440354

440354
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

463206
type: SpeciesReference
stoichiometry: 1.0
species: 443074

439694
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.161E-16
initial amount: NaN
in compartment: 439494

443913
type: Reaction
kinetic law: 463677
product: 463665
reactant: 463653
reactant: 463641
notes: The rate consts give a total binding affinity of only
fast: false
reversible: true

463677
type: KineticLaw
local parameters: 352844
local parameters: 352843
notes: kf*Gq_slash_Rec_minus_Gq*Gq_slash_mGluRAntag-kb*Gq_slash_Blocked_minus_rec_minus_Gq

352844
type: LocalParameter
units: 462030
value: 1.5E-17

352843
type: LocalParameter
units: 462115
value: 9.000045E-14

463665
type: SpeciesReference
stoichiometry: 1.0
species: 440534

440534
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

463653
type: SpeciesReference
stoichiometry: 1.0
species: 443234

443234
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: 439494

463641
type: SpeciesReference
stoichiometry: 1.0
species: 440494

440494
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

443214
type: Species
constant: true
boundary condition: true
has only substance units: false
initial concentration: 10.0
initial amount: NaN
in compartment: 439494

441294
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

440894
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

444393
type: Reaction
kinetic law: 464764
product: 464752
reactant: 464740
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

464764
type: KineticLaw
local parameters: 352916
local parameters: 352913
notes: kf*CaM_slash_neurogranin_star_-kb*CaM_slash_neurogranin

352916
type: LocalParameter
units: 462030
value: 0.0

352913
type: LocalParameter
units: 462030
value: 7.5E-18

464752
type: SpeciesReference
stoichiometry: 1.0
species: 442134

464740
type: SpeciesReference
stoichiometry: 1.0
species: 442114

442114
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

442554
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

445133
type: Reaction
kinetic law: 466527
product: 466515
product: 466503
reactant: 466490
fast: false
reversible: false

466527
type: KineticLaw
local parameters: 353003
notes: k3*PLA2_slash_PLA2_minus_Ca_star__slash_kenz_slash_kenz_cplx

353003
type: LocalParameter
units: 462030
value: 8.1E-15

466515
type: SpeciesReference
stoichiometry: 1.0
species: 439934

466503
type: SpeciesReference
stoichiometry: 1.0
species: 439774

466490
type: SpeciesReference
stoichiometry: 1.0
species: 439954

445933
type: Reaction
kinetic law: 468497
product: 468485
product: 468473
reactant: 468461
fast: false
reversible: false

353081
type: LocalParameter
units: 462030
value: 9.0E-15

468485
type: SpeciesReference
stoichiometry: 1.0
species: 440934

468473
type: SpeciesReference
stoichiometry: 1.0
species: 440594

440594
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 439494

468461
type: SpeciesReference
stoichiometry: 1.0
species: 440994

440994
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

442294
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

447033
type: Reaction
kinetic law: 471191
modifier: 471178
product: 471166
reactant: 471154
fast: false
reversible: false

471191
type: KineticLaw
local parameters: 353291
local parameters: 353288
notes: kcat*AC_slash_AC1_minus_CaM*AC_slash_ATP/(Km+AC_slash_ATP)

353291
type: LocalParameter
units: 461994
value: 20.0

353288
type: LocalParameter
units: 462030
value: 2.7E-14

442734
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

471166
type: SpeciesReference
stoichiometry: 1.0
species: 442714

471154
type: SpeciesReference
stoichiometry: 1.0
species: 443274

442754
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.02
initial amount: NaN
in compartment: 439494

444853
type: Reaction
kinetic law: 465838
product: 465826
reactant: 465814
fast: false
reversible: true

465838
type: KineticLaw
local parameters: 352976
local parameters: 352975
notes: kf*Ca_input-kb*Ca

352976
type: LocalParameter
units: 462030
value: 1.5E-13

352975
type: LocalParameter
units: 462030
value: 1.5E-13

465826
type: SpeciesReference
stoichiometry: 1.0
species: 443074

465814
type: SpeciesReference
stoichiometry: 1.0
species: 443094

443094
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

441234
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

444233
type: Reaction
kinetic law: 464400
product: 464388
reactant: 464376
fast: false
reversible: true

464400
type: KineticLaw
local parameters: 352892
local parameters: 352891
notes: kf*PLC_g_slash_Ca_dot_PLC_g_star_-kb*PLC_g_slash_Ca_dot_PLC_g

352892
type: LocalParameter
units: 462030
value: 0.0

352891
type: LocalParameter
units: 462030
value: 7.5E-17

464388
type: SpeciesReference
stoichiometry: 1.0
species: 441714

464376
type: SpeciesReference
stoichiometry: 1.0
species: 441734

441314
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

444873
type: Reaction
kinetic law: 465886
product: 465874
reactant: 465862
reactant: 465850
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

465886
type: KineticLaw
local parameters: 352978
local parameters: 352977
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

352978
type: LocalParameter
units: 462030
value: 2.4E-14

352977
type: LocalParameter
units: 462115
value: 4.499955E-16

465874
type: SpeciesReference
stoichiometry: 1.0
species: 439794

465862
type: SpeciesReference
stoichiometry: 1.0
species: 443294

465850
type: SpeciesReference
stoichiometry: 1.0
species: 440554

440514
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

447053
type: Reaction
kinetic law: 471240
modifier: 471228
product: 471216
reactant: 471203
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

471240
type: KineticLaw
local parameters: 353297
local parameters: 353294
notes: kcat*AC_slash_AC2_star_*AC_slash_ATP/(Km+AC_slash_ATP)

353297
type: LocalParameter
units: 461994
value: 20.1152893440692

353294
type: LocalParameter
units: 462030
value: 1.05E-14

471216
type: SpeciesReference
stoichiometry: 1.0
species: 442714

471203
type: SpeciesReference
stoichiometry: 1.0
species: 443274

445213
type: Reaction
kinetic law: 466720
product: 466708
product: 466696
reactant: 466684
fast: false
reversible: false

466720
type: KineticLaw
local parameters: 353009
notes: k3*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx

353009
type: LocalParameter
units: 462030
value: 5.4E-14

466708
type: SpeciesReference
stoichiometry: 1.0
species: 440014

440014
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

466696
type: SpeciesReference
stoichiometry: 1.0
species: 439774

466684
type: SpeciesReference
stoichiometry: 1.0
species: 440034

447153
type: Reaction
kinetic law: 471481
product: 471469
product: 471457
reactant: 471445
fast: false
reversible: false

471481
type: KineticLaw
local parameters: 353324
notes: k3*AC_slash_cAMP_minus_PDE_slash_PDE_slash_PDE_cplx

353324
type: LocalParameter
units: 462030
value: 1.5E-14

471469
type: SpeciesReference
stoichiometry: 1.0
species: 442894

471457
type: SpeciesReference
stoichiometry: 1.0
species: 442854

442854
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 325493.333333333
initial amount: NaN
in compartment: 439514

471445
type: SpeciesReference
stoichiometry: 1.0
species: 442914

442654
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

440214
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

444413
type: Reaction
kinetic law: 464812
product: 464800
reactant: 464788
reactant: 464776
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

464812
type: KineticLaw
local parameters: 352918
local parameters: 352917
notes: kf*PP1_slash_I1_star_*PP1_minus_active-kb*PP1_slash_PP1_minus_I1_star_

352918
type: LocalParameter
units: 462030
value: 1.5E-16

352917
type: LocalParameter
units: 462115
value: 7.499655E-13

464800
type: SpeciesReference
stoichiometry: 1.0
species: 442294

464788
type: SpeciesReference
stoichiometry: 1.0
species: 441954

464776
type: SpeciesReference
stoichiometry: 1.0
species: 442274

444093
type: Reaction
kinetic law: 464087
product: 464075
reactant: 464063
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

464087
type: KineticLaw
local parameters: 352874
local parameters: 352873
notes: kf*EGFR_slash_L_dot_EGFR-kb*EGFR_slash_Internal_L_dot_EGFR

352874
type: LocalParameter
units: 462030
value: 4.95E-19

352873
type: LocalParameter
units: 462030
value: 3.0E-18

464075
type: SpeciesReference
stoichiometry: 1.0
species: 441554

464063
type: SpeciesReference
stoichiometry: 1.0
species: 441454

447233
type: Reaction
kinetic law: 471673
product: 471661
product: 471649
reactant: 471637
fast: false
reversible: false

471673
type: KineticLaw
local parameters: 353342
notes: k3*AC_slash_PDE1_slash_PDE1_slash_PDE1_cplx

353342
type: LocalParameter
units: 462030
value: 2.5005E-15

471661
type: SpeciesReference
stoichiometry: 1.0
species: 442974

471649
type: SpeciesReference
stoichiometry: 1.0
species: 442854

471637
type: SpeciesReference
stoichiometry: 1.0
species: 442994

444433
type: Reaction
kinetic law: 464861
product: 464849
product: 464836
reactant: 464824
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

464861
type: KineticLaw
local parameters: 352922
local parameters: 352919
notes: kf*PP1_slash_PP1_minus_I1-kb*PP1_minus_active*PP1_slash_I1

352922
type: LocalParameter
units: 462115
value: 0.0

352919
type: LocalParameter
units: 462030
value: 1.5E-15

464849
type: SpeciesReference
stoichiometry: 1.0
species: 442254

464836
type: SpeciesReference
stoichiometry: 1.0
species: 441954

464824
type: SpeciesReference
stoichiometry: 1.0
species: 442314

442314
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

445353
type: Reaction
kinetic law: 467058
product: 467045
reactant: 467033
reactant: 467021
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

467058
type: KineticLaw
local parameters: 353026
local parameters: 353023
notes: k1*MAPK_slash_craf_minus_1_star_*MAPK_star_-k2*MAPK_star__slash_MAPK_star__minus_feedback_slash_MAPK_star__minus_feedback_cplx

353026
type: LocalParameter
units: 462030
value: 6.0E-14

353023
type: LocalParameter
units: 462115
value: 2.925045E-15

467045
type: SpeciesReference
stoichiometry: 1.0
species: 440194

467033
type: SpeciesReference
stoichiometry: 1.0
species: 440154

467021
type: SpeciesReference
stoichiometry: 1.0
species: 440574

444973
type: Reaction
kinetic law: 466127
product: 466115
product: 466103
reactant: 466091
fast: false
reversible: false

466127
type: KineticLaw
local parameters: 352985
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_GEF_slash_PKC_minus_act_minus_GEF_cplx

352985
type: LocalParameter
units: 462030
value: 6.0E-15

466115
type: SpeciesReference
stoichiometry: 1.0
species: 443294

466103
type: SpeciesReference
stoichiometry: 1.0
species: 441094

466091
type: SpeciesReference
stoichiometry: 1.0
species: 439834

439834
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

444353
type: Reaction
kinetic law: 464680
product: 464668
reactant: 464656
reactant: 464644
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

464680
type: KineticLaw
local parameters: 352910
local parameters: 352907
notes: kf*CaM_minus_Ca3*Ca-kb*CaM_minus_Ca4

352910
type: LocalParameter
units: 462030
value: 1.5E-14

352907
type: LocalParameter
units: 462115
value: 6.975045E-16

464668
type: SpeciesReference
stoichiometry: 1.0
species: 441374

464656
type: SpeciesReference
stoichiometry: 1.0
species: 443074

464644
type: SpeciesReference
stoichiometry: 1.0
species: 442154

442154
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

447253
type: Reaction
kinetic law: 471721
product: 471709
reactant: 471697
reactant: 471685
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

471721
type: KineticLaw
local parameters: 353348
local parameters: 353345
notes: k1*cAMP*AC_slash_CaM_dot_PDE1-k2*AC_slash_CaM_dot_PDE1_slash_CaM_dot_PDE1_slash_CaM_dot_PDE1_cplx

353348
type: LocalParameter
units: 462030
value: 6.0E-14

353345
type: LocalParameter
units: 462115
value: 1.89E-15

471709
type: SpeciesReference
stoichiometry: 1.0
species: 443034

471697
type: SpeciesReference
stoichiometry: 1.0
species: 443014

443014
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

471685
type: SpeciesReference
stoichiometry: 1.0
species: 442714

444693
type: Reaction
kinetic law: 465487
product: 465475
reactant: 465463
reactant: 465451
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

465487
type: KineticLaw
local parameters: 352958
local parameters: 352955
notes: kf*CaM_minus_Ca4*AC_slash_AC1-kb*AC_slash_AC1_minus_CaM

352958
type: LocalParameter
units: 462030
value: 1.5E-15

352955
type: LocalParameter
units: 462115
value: 7.499925E-14

465475
type: SpeciesReference
stoichiometry: 1.0
species: 442734

465463
type: SpeciesReference
stoichiometry: 1.0
species: 442754

465451
type: SpeciesReference
stoichiometry: 1.0
species: 441374

442494
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

444993
type: Reaction
kinetic law: 466175
product: 466163
reactant: 466151
reactant: 466139
notes: Rates from Huang et al ABB 305:2 570-580 1993
fast: false
reversible: true

466175
type: KineticLaw
local parameters: 352990
local parameters: 352987
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

352990
type: LocalParameter
units: 462030
value: 3.51E-15

352987
type: LocalParameter
units: 462115
value: 1.529955E-16

466163
type: SpeciesReference
stoichiometry: 1.0
species: 439854

439854
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

466151
type: SpeciesReference
stoichiometry: 1.0
species: 443294

466139
type: SpeciesReference
stoichiometry: 1.0
species: 442134

440394
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

447273
type: Reaction
kinetic law: 471770
product: 471757
product: 471745
reactant: 471733
fast: false
reversible: false

471770
type: KineticLaw
local parameters: 353351
notes: k3*AC_slash_CaM_dot_PDE1_slash_CaM_dot_PDE1_slash_CaM_dot_PDE1_cplx

353351
type: LocalParameter
units: 462030
value: 1.5E-14

471757
type: SpeciesReference
stoichiometry: 1.0
species: 443014

471745
type: SpeciesReference
stoichiometry: 1.0
species: 442854

471733
type: SpeciesReference
stoichiometry: 1.0
species: 443034

444533
type: Reaction
kinetic law: 465102
product: 465090
reactant: 465078
reactant: 465066
fast: false
reversible: true

465102
type: KineticLaw
local parameters: 352934
local parameters: 352933
notes: kf*CaM_minus_Ca4*CaNAB_minus_Ca4-kb*PP2B_slash_CaMCa4_minus_CaNAB

352934
type: LocalParameter
units: 462030
value: 1.5E-15

352933
type: LocalParameter
units: 462115
value: 9.000045E-13

465090
type: SpeciesReference
stoichiometry: 1.0
species: 442514

442514
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

465078
type: SpeciesReference
stoichiometry: 1.0
species: 442394

465066
type: SpeciesReference
stoichiometry: 1.0
species: 441374

446193
type: Reaction
kinetic law: 469124
product: 469112
reactant: 469100
reactant: 469088
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

469124
type: KineticLaw
local parameters: 353110
local parameters: 353107
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

353110
type: LocalParameter
units: 462030
value: 5.4E-14

353107
type: LocalParameter
units: 462115
value: 9.000045E-15

469112
type: SpeciesReference
stoichiometry: 1.0
species: 441334

441334
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

469100
type: SpeciesReference
stoichiometry: 1.0
species: 441294

469088
type: SpeciesReference
stoichiometry: 1.0
species: 442254

446473
type: Reaction
kinetic law: 469828
product: 469816
reactant: 469804
reactant: 469792
fast: false
reversible: true

469828
type: KineticLaw
local parameters: 353165
local parameters: 353162
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

353165
type: LocalParameter
units: 462030
value: 3.0E-15

353162
type: LocalParameter
units: 462115
value: 3.30102E-17

469816
type: SpeciesReference
stoichiometry: 1.0
species: 441894

441894
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

469804
type: SpeciesReference
stoichiometry: 1.0
species: 443314

469792
type: SpeciesReference
stoichiometry: 1.0
species: 441774

444633
type: Reaction
kinetic law: 465343
product: 465331
product: 465319
reactant: 465307
notes: This has to be fast, as the activation of PKA by cAMP is also fast. kf was 10
fast: false
reversible: true

465343
type: KineticLaw
local parameters: 352948
local parameters: 352947
notes: kf*PKA_slash_R2C2_minus_cAMP4-kb*PKA_minus_active*PKA_slash_R2C_minus_cAMP4

352948
type: LocalParameter
units: 462115
value: 2.7E-14

352947
type: LocalParameter
units: 462030
value: 9.0E-14

465331
type: SpeciesReference
stoichiometry: 1.0
species: 442634

442634
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

465319
type: SpeciesReference
stoichiometry: 1.0
species: 441294

465307
type: SpeciesReference
stoichiometry: 1.0
species: 442614

442614
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

440814
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

444553
type: Reaction
kinetic law: 465150
product: 465138
reactant: 465126
reactant: 465114
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

465150
type: KineticLaw
local parameters: 352938
local parameters: 352935
notes: kf*PKA_slash_R2C2*cAMP-kb*PKA_slash_R2C2_minus_cAMP

352938
type: LocalParameter
units: 462030
value: 4.95E-14

352935
type: LocalParameter
units: 462115
value: 8.1E-14

465138
type: SpeciesReference
stoichiometry: 1.0
species: 442554

465126
type: SpeciesReference
stoichiometry: 1.0
species: 442714

465114
type: SpeciesReference
stoichiometry: 1.0
species: 442534

442534
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 439494

445893
type: Reaction
kinetic law: 468401
product: 468389
product: 468377
reactant: 468365
fast: false
reversible: false

353078
type: LocalParameter
units: 462030
value: 9.0E-15

468389
type: SpeciesReference
stoichiometry: 1.0
species: 440934

468377
type: SpeciesReference
stoichiometry: 1.0
species: 440734

468365
type: SpeciesReference
stoichiometry: 1.0
species: 440974

440974
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

446153
type: Reaction
kinetic law: 469028
product: 469016
reactant: 469004
reactant: 468992
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

469028
type: KineticLaw
local parameters: 353104
local parameters: 353103
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

353104
type: LocalParameter
units: 462030
value: 5.4E-14

353103
type: LocalParameter
units: 462115
value: 9.000045E-15

469016
type: SpeciesReference
stoichiometry: 1.0
species: 441314

469004
type: SpeciesReference
stoichiometry: 1.0
species: 441294

468992
type: SpeciesReference
stoichiometry: 1.0
species: 441074

441074
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.1
initial amount: NaN
in compartment: 439494

444653
type: Reaction
kinetic law: 465391
product: 465379
product: 465367
reactant: 465355
fast: false
reversible: true

465391
type: KineticLaw
local parameters: 352952
local parameters: 352949
notes: kf*PKA_slash_R2C_minus_cAMP4-kb*PKA_minus_active*PKA_slash_R2_minus_cAMP4

352952
type: LocalParameter
units: 462115
value: 2.7E-14

352949
type: LocalParameter
units: 462030
value: 9.0E-14

465379
type: SpeciesReference
stoichiometry: 1.0
species: 442654

465367
type: SpeciesReference
stoichiometry: 1.0
species: 441294

465355
type: SpeciesReference
stoichiometry: 1.0
species: 442634

444713
type: Reaction
kinetic law: 465524
product: 465511
reactant: 465499
notes: Random rate.
fast: false
reversible: true

465524
type: KineticLaw
local parameters: 352960
local parameters: 352959
notes: kf*AC_slash_AC2_star_-kb*AC_slash_AC2

352960
type: LocalParameter
units: 462030
value: 0.0

352959
type: LocalParameter
units: 462030
value: 1.5E-16

465511
type: SpeciesReference
stoichiometry: 1.0
species: 442814

465499
type: SpeciesReference
stoichiometry: 1.0
species: 442774

444573
type: Reaction
kinetic law: 465199
product: 465187
reactant: 465175
reactant: 465162
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

465199
type: KineticLaw
local parameters: 352940
local parameters: 352939
notes: kf*PKA_slash_R2C2_minus_cAMP*cAMP-kb*PKA_slash_R2C2_minus_cAMP2

352940
type: LocalParameter
units: 462030
value: 4.95E-14

352939
type: LocalParameter
units: 462115
value: 8.1E-14

465187
type: SpeciesReference
stoichiometry: 1.0
species: 442574

442574
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

465175
type: SpeciesReference
stoichiometry: 1.0
species: 442714

465162
type: SpeciesReference
stoichiometry: 1.0
species: 442554

439554
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 4.91366666666667E-18
initial amount: NaN
in compartment: 439494

444833
type: Reaction
kinetic law: 465802
product: 465790
reactant: 465778
reactant: 465766
notes: 18 May 2003. This reaction is here to provide basal activity for MAPK as well as the potential for direct EGF stimulus without PKC activation. Based on model from FB/fb28c.g: the model used for MKP-1 turnover. The rates there were constrained by basal activity values.
fast: false
reversible: true

465802
type: KineticLaw
local parameters: 352974
local parameters: 352973
notes: kf*MAPK_slash_craf_minus_1*Ras_slash_GTP_minus_Ras-kb*MAPK_slash_Raf_minus_GTP_minus_Ras

352974
type: LocalParameter
units: 462030
value: 1.5E-15

352973
type: LocalParameter
units: 462115
value: 9.000045E-15

465790
type: SpeciesReference
stoichiometry: 1.0
species: 440754

465778
type: SpeciesReference
stoichiometry: 1.0
species: 441134

441134
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

465766
type: SpeciesReference
stoichiometry: 1.0
species: 440554

446593
type: Reaction
kinetic law: 470118
product: 470106
reactant: 470094
reactant: 470082
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

470118
type: KineticLaw
local parameters: 353192
local parameters: 353189
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

353192
type: LocalParameter
units: 462030
value: 2.1E-15

353189
type: LocalParameter
units: 462115
value: 5.147955E-16

470106
type: SpeciesReference
stoichiometry: 1.0
species: 441974

441974
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

470094
type: SpeciesReference
stoichiometry: 1.0
species: 441954

470082
type: SpeciesReference
stoichiometry: 1.0
species: 441794

444753
type: Reaction
kinetic law: 465621
product: 465609
reactant: 465597
reactant: 465584
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

465621
type: KineticLaw
local parameters: 352966
local parameters: 352965
notes: kf*Gs_minus_alpha*AC_slash_AC1-kb*AC_slash_AC1_minus_Gs

352966
type: LocalParameter
units: 462030
value: 1.5E-15

352965
type: LocalParameter
units: 462115
value: 1.89E-13

465609
type: SpeciesReference
stoichiometry: 1.0
species: 442834

465597
type: SpeciesReference
stoichiometry: 1.0
species: 442754

465584
type: SpeciesReference
stoichiometry: 1.0
species: 443054

447113
type: Reaction
kinetic law: 471385
modifier: 471373
product: 471361
reactant: 471349
fast: false
reversible: false

471385
type: KineticLaw
local parameters: 353315
local parameters: 353312
notes: kcat*AC_slash_AC2_star__minus_Gs*AC_slash_ATP/(Km+AC_slash_ATP)

353315
type: LocalParameter
units: 461994
value: 60.0

353312
type: LocalParameter
units: 462030
value: 8.1E-14

471361
type: SpeciesReference
stoichiometry: 1.0
species: 442714

471349
type: SpeciesReference
stoichiometry: 1.0
species: 443274

445713
type: Reaction
kinetic law: 467967
product: 467955
reactant: 467943
reactant: 467931
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

467967
type: KineticLaw
local parameters: 353062
local parameters: 353059
notes: k1*MAPK_slash_MAPKK_minus_ser*MAPK_slash_Raf_star__minus_GTP_minus_Ras-k2*MAPK_slash_Raf_star__minus_GTP_minus_Ras_slash_Raf_star__minus_GTP_minus_Ras_dot_2_slash_Raf_star__minus_GTP_minus_Ras_dot_2_cplx

353062
type: LocalParameter
units: 462030
value: 1.8E-15

353059
type: LocalParameter
units: 462115
value: 1.41426E-14

467955
type: SpeciesReference
stoichiometry: 1.0
species: 440854

467943
type: SpeciesReference
stoichiometry: 1.0
species: 440814

467931
type: SpeciesReference
stoichiometry: 1.0
species: 440734

446693
type: Reaction
kinetic law: 470363
product: 470351
product: 470338
reactant: 470325
fast: false
reversible: false

470363
type: KineticLaw
local parameters: 353213
notes: k3*PP1_minus_active_slash_Deph_minus_thr306_slash_Deph_minus_thr306_cplx

353213
type: LocalParameter
units: 462030
value: 5.25E-16

470351
type: SpeciesReference
stoichiometry: 1.0
species: 441954

470338
type: SpeciesReference
stoichiometry: 1.0
species: 441754

470325
type: SpeciesReference
stoichiometry: 1.0
species: 442014

444773
type: Reaction
kinetic law: 465669
product: 465657
reactant: 465645
reactant: 465633
notes: kb/kf = 1.2 nM so kf = kb/720 = 1.3888 * kb.
fast: false
reversible: true

465669
type: KineticLaw
local parameters: 352968
local parameters: 352967
notes: kf*Gs_minus_alpha*AC_slash_AC2_star_-kb*AC_slash_AC2_star__minus_Gs

352968
type: LocalParameter
units: 462030
value: 1.5E-15

352967
type: LocalParameter
units: 462115
value: 1.2499245E-12

465657
type: SpeciesReference
stoichiometry: 1.0
species: 442874

465645
type: SpeciesReference
stoichiometry: 1.0
species: 442774

465633
type: SpeciesReference
stoichiometry: 1.0
species: 443054

444253
type: Reaction
kinetic law: 464448
product: 464436
reactant: 464424
reactant: 464412
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

464448
type: KineticLaw
local parameters: 352896
local parameters: 352893
notes: kf*CaM_minus_Ca4*CaMKII_slash_CaMKII-kb*CaMKII_slash_CaMKII_minus_CaM

352896
type: LocalParameter
units: 462030
value: 7.5E-15

352893
type: LocalParameter
units: 462115
value: 7.499925E-14

464436
type: SpeciesReference
stoichiometry: 1.0
species: 441774

464424
type: SpeciesReference
stoichiometry: 1.0
species: 441754

464412
type: SpeciesReference
stoichiometry: 1.0
species: 441374

444013
type: Reaction
kinetic law: 463930
product: 463918
reactant: 463906
reactant: 463894
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

463930
type: KineticLaw
local parameters: 352862
local parameters: 352861
notes: kf*Ras_slash_inact_minus_GEF*CaM_minus_Ca4-kb*Ras_slash_CaM_minus_GEF

352862
type: LocalParameter
units: 462030
value: 1.5E-15

352861
type: LocalParameter
units: 462115
value: 9.000045E-14

463918
type: SpeciesReference
stoichiometry: 1.0
species: 441254

441254
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

463906
type: SpeciesReference
stoichiometry: 1.0
species: 441374

463894
type: SpeciesReference
stoichiometry: 1.0
species: 441074

446373
type: Reaction
kinetic law: 469562
product: 469550
product: 469538
reactant: 469526
fast: false
reversible: false

469562
type: KineticLaw
local parameters: 353140
notes: k3*EGFR_slash_L_dot_EGFR_slash_phosph_Shc_slash_phosph_Shc_cplx

353140
type: LocalParameter
units: 462030
value: 3.0E-16

469550
type: SpeciesReference
stoichiometry: 1.0
species: 441454

469538
type: SpeciesReference
stoichiometry: 1.0
species: 441534

469526
type: SpeciesReference
stoichiometry: 1.0
species: 441494

441494
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

443693
type: Reaction
kinetic law: 462761
product: 462749
reactant: 462737
reactant: 462725
fast: false
reversible: true

462761
type: KineticLaw
local parameters: 352786
local parameters: 352785
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star_

352786
type: LocalParameter
units: 462030
value: 1.5E-16

352785
type: LocalParameter
units: 462115
value: 1.799955E-17

462749
type: SpeciesReference
stoichiometry: 1.0
species: 440014

462737
type: SpeciesReference
stoichiometry: 1.0
species: 439934

462725
type: SpeciesReference
stoichiometry: 1.0
species: 443134

443134
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: 439494

443654
type: Reaction
kinetic law: 462665
product: 462653
reactant: 462640
reactant: 462628
notes: Leslie and Channon BBA 1045 (1990) 261-270 fig6 pp267.
fast: false
reversible: true

462665
type: KineticLaw
local parameters: 352780
local parameters: 352779
notes: kf*PLA2_slash_PLA2_minus_cytosolic*Ca-kb*PLA2_slash_PLA2_minus_Ca_star_

352780
type: LocalParameter
units: 462030
value: 1.5E-16

352779
type: LocalParameter
units: 462115
value: 1.499985E-15

462653
type: SpeciesReference
stoichiometry: 1.0
species: 439934

462640
type: SpeciesReference
stoichiometry: 1.0
species: 443074

462628
type: SpeciesReference
stoichiometry: 1.0
species: 439914

443674
type: Reaction
kinetic law: 462713
product: 462701
reactant: 462689
reactant: 462677
fast: false
reversible: true

462713
type: KineticLaw
local parameters: 352784
local parameters: 352781
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_cytosolic-kb*PLA2_slash_PIP2_minus_PLA2_star_

352784
type: LocalParameter
units: 462030
value: 7.5E-16

352781
type: LocalParameter
units: 462115
value: 1.799955E-18

462701
type: SpeciesReference
stoichiometry: 1.0
species: 439974

439974
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

462689
type: SpeciesReference
stoichiometry: 1.0
species: 439914

462677
type: SpeciesReference
stoichiometry: 1.0
species: 443134

442434
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 439494

447013
type: Reaction
kinetic law: 471142
product: 471130
product: 471117
reactant: 471104
fast: false
reversible: false

471142
type: KineticLaw
local parameters: 353285
notes: k3*CaNAB_minus_Ca4_slash_dephosph_inhib1_noCaM_slash_dephosph_inhib1_noCaM_cplx

353285
type: LocalParameter
units: 462030
value: 5.1E-17

471130
type: SpeciesReference
stoichiometry: 1.0
species: 442394

471117
type: SpeciesReference
stoichiometry: 1.0
species: 442254

471104
type: SpeciesReference
stoichiometry: 1.0
species: 442414

442414
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

444213
type: Reaction
kinetic law: 464364
product: 464351
reactant: 464339
reactant: 464327
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

464364
type: KineticLaw
local parameters: 352890
local parameters: 352889
notes: kf*Ca*PLC_g_slash_PLC_G_star_-kb*PLC_g_slash_Ca_dot_PLC_g_star_

352890
type: LocalParameter
units: 462030
value: 1.5E-14

352889
type: LocalParameter
units: 462115
value: 1.799955E-14

464351
type: SpeciesReference
stoichiometry: 1.0
species: 441734

464339
type: SpeciesReference
stoichiometry: 1.0
species: 441694

441694
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

464327
type: SpeciesReference
stoichiometry: 1.0
species: 443074

446293
type: Reaction
kinetic law: 469368
product: 469356
product: 469344
reactant: 469332
fast: false
reversible: false

469368
type: KineticLaw
local parameters: 353122
notes: k3*Shc_star__dot_Sos_dot_Grb2_slash_Sos_dot_Ras_GEF_slash_Sos_dot_Ras_GEF_cplx

353122
type: LocalParameter
units: 462030
value: 3.0E-17

469356
type: SpeciesReference
stoichiometry: 1.0
species: 441394

441394
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

469344
type: SpeciesReference
stoichiometry: 1.0
species: 441134

469332
type: SpeciesReference
stoichiometry: 1.0
species: 441414

441414
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

440834
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

441994
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

440474
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

446873
type: Reaction
kinetic law: 470800
product: 470788
reactant: 470776
reactant: 470764
fast: false
reversible: true

470800
type: KineticLaw
local parameters: 353255
local parameters: 353252
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

353255
type: LocalParameter
units: 462030
value: 2.04E-15

353252
type: LocalParameter
units: 462115
value: 5.13E-16

470788
type: SpeciesReference
stoichiometry: 1.0
species: 442234

470776
type: SpeciesReference
stoichiometry: 1.0
species: 443354

470764
type: SpeciesReference
stoichiometry: 1.0
species: 442294

444373
type: Reaction
kinetic law: 464728
product: 464716
reactant: 464704
reactant: 464692
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

464728
type: KineticLaw
local parameters: 352912
local parameters: 352911
notes: kf*CaM_slash_neurogranin*CaM_slash_CaM-kb*CaM_slash_neurogranin_minus_CaM

352912
type: LocalParameter
units: 462030
value: 1.5E-15

352911
type: LocalParameter
units: 462115
value: 4.499955E-16

464716
type: SpeciesReference
stoichiometry: 1.0
species: 442094

464704
type: SpeciesReference
stoichiometry: 1.0
species: 442074

442074
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 20.0
initial amount: NaN
in compartment: 439494

464692
type: SpeciesReference
stoichiometry: 1.0
species: 442134

444133
type: Reaction
kinetic law: 464183
product: 464171
reactant: 464159
reactant: 464147
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

464183
type: KineticLaw
local parameters: 352880
local parameters: 352877
notes: kf*Sos_slash_Sos_star_*Sos_slash_Grb2-kb*Sos_slash_Sos_star__dot_Grb2

352880
type: LocalParameter
units: 462030
value: 2.52E-17

352877
type: LocalParameter
units: 462115
value: 3.75003E-17

464171
type: SpeciesReference
stoichiometry: 1.0
species: 441574

441574
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

464159
type: SpeciesReference
stoichiometry: 1.0
species: 441594

464147
type: SpeciesReference
stoichiometry: 1.0
species: 441634

441634
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

443774
type: Reaction
kinetic law: 463098
product: 463086
reactant: 463074
reactant: 463062
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

463098
type: KineticLaw
local parameters: 352810
local parameters: 352807
notes: kf*G_star_GTP*PLCbeta_slash_PLC_minus_Ca-kb*PLCbeta_slash_PLC_minus_Ca_minus_Gq

352810
type: LocalParameter
units: 462030
value: 1.5E-15

352807
type: LocalParameter
units: 462115
value: 3.78E-14

463086
type: SpeciesReference
stoichiometry: 1.0
species: 440314

463074
type: SpeciesReference
stoichiometry: 1.0
species: 440274

440274
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

463062
type: SpeciesReference
stoichiometry: 1.0
species: 440394

444473
type: Reaction
kinetic law: 464957
product: 464945
reactant: 464933
reactant: 464921
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

464957
type: KineticLaw
local parameters: 352928
local parameters: 352925
notes: kf*PP2B_slash_CaNAB*Ca^2-kb*PP2B_slash_CaNAB_minus_Ca2

352928
type: LocalParameter
units: 462030
value: 1.5E-15

352925
type: LocalParameter
units: 462067
value: 1.501254E-11

464945
type: SpeciesReference
stoichiometry: 1.0
species: 442454

464933
type: SpeciesReference
stoichiometry: 2.0
species: 443074

464921
type: SpeciesReference
stoichiometry: 1.0
species: 442434

443874
type: Reaction
product: 463544
fast: false
reversible: true
notes: This is the kcat==k3 stage of the Rec-Glu ezymatic activation of Gq. From Berstein et al actiation is at .35 - 0.7/min From Fay et al Biochem 30 5066-5075 1991 kf = .01/sec From Nakamura et al J physiol Lond 474:1 35-41 1994 see time courses. Also (Berstein) 15-40% of gprot is in GTP-bound form on stim.
product: 463569
reactant: 463532
product: 463557
kinetic law: 463581

463544
type: SpeciesReference
stoichiometry: 1.0
species: 440394

463569
type: SpeciesReference
stoichiometry: 1.0
species: 440474

463532
type: SpeciesReference
stoichiometry: 1.0
species: 440514

463557
type: SpeciesReference
stoichiometry: 1.0
species: 440374

463581
type: KineticLaw
local parameters: 352838
local parameters: 352837
notes: kf*Gq_slash_Rec_minus_Glu_minus_Gq-kb*G_star_GTP*BetaGamma*Gq_slash_Rec_minus_Glu

352838
type: LocalParameter
units: 462067
value: 0.0

352837
type: LocalParameter
units: 462030
value: 1.5E-17

443794
type: Reaction
kinetic law: 463194
product: 463182
reactant: 463170
reactant: 463158
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

463194
type: KineticLaw
local parameters: 352816
local parameters: 352813
notes: kf*PLCbeta_slash_PLC*G_star_GTP-kb*PLCbeta_slash_PLC_minus_Gq

352816
type: LocalParameter
units: 462030
value: 1.5E-15

352813
type: LocalParameter
units: 462115
value: 3.78E-15

463182
type: SpeciesReference
stoichiometry: 1.0
species: 440354

463170
type: SpeciesReference
stoichiometry: 1.0
species: 440394

463158
type: SpeciesReference
stoichiometry: 1.0
species: 440254

440254
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.8
initial amount: NaN
in compartment: 439494

446653
type: Reaction
kinetic law: 470265
product: 470252
product: 470240
reactant: 470228
fast: false
reversible: false

470265
type: KineticLaw
local parameters: 353204
notes: k3*PP1_minus_active_slash_Deph_minus_thr305_slash_Deph_minus_thr305_cplx

353204
type: LocalParameter
units: 462030
value: 5.25E-16

470252
type: SpeciesReference
stoichiometry: 1.0
species: 441954

470240
type: SpeciesReference
stoichiometry: 1.0
species: 441834

470228
type: SpeciesReference
stoichiometry: 1.0
species: 441994

444933
type: Reaction
kinetic law: 466031
product: 466019
product: 466007
reactant: 465995
fast: false
reversible: false

466031
type: KineticLaw
local parameters: 352982
notes: k3*PKC_minus_active_slash_PKC_minus_inact_minus_GAP_slash_PKC_minus_inact_minus_GAP_cplx

352982
type: LocalParameter
units: 462030
value: 6.0E-15

466019
type: SpeciesReference
stoichiometry: 1.0
species: 443294

466007
type: SpeciesReference
stoichiometry: 1.0
species: 441174

441174
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

465995
type: SpeciesReference
stoichiometry: 1.0
species: 439814

439814
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

444813
type: Reaction
kinetic law: 465754
product: 465741
reactant: 465729
reactant: 465717
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

465754
type: KineticLaw
local parameters: 352972
local parameters: 352971
notes: kf*AC_slash_PDE1*CaM_minus_Ca4-kb*AC_slash_CaM_dot_PDE1

352972
type: LocalParameter
units: 462030
value: 7.5E-15

352971
type: LocalParameter
units: 462115
value: 1.08E-12

465741
type: SpeciesReference
stoichiometry: 1.0
species: 443014

465729
type: SpeciesReference
stoichiometry: 1.0
species: 441374

465717
type: SpeciesReference
stoichiometry: 1.0
species: 442974

444313
type: Reaction
kinetic law: 464583
product: 464571
reactant: 464559
reactant: 464547
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

464583
type: KineticLaw
local parameters: 352904
local parameters: 352903
notes: kf*CaM_slash_CaM*Ca^2-kb*CaM_minus_TR2_minus_Ca2

352904
type: LocalParameter
units: 462030
value: 1.08E-13

352903
type: LocalParameter
units: 462067
value: 1.08000135E-13

464571
type: SpeciesReference
stoichiometry: 1.0
species: 442174

442174
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

464559
type: SpeciesReference
stoichiometry: 2.0
species: 443074

464547
type: SpeciesReference
stoichiometry: 1.0
species: 442074

444333
type: Reaction
kinetic law: 464632
product: 464620
reactant: 464608
reactant: 464596
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

464632
type: KineticLaw
local parameters: 352906
local parameters: 352905
notes: kf*CaM_minus_TR2_minus_Ca2*Ca-kb*CaM_minus_Ca3

352906
type: LocalParameter
units: 462030
value: 1.5E-14

352905
type: LocalParameter
units: 462115
value: 5.4E-15

464620
type: SpeciesReference
stoichiometry: 1.0
species: 442154

464608
type: SpeciesReference
stoichiometry: 1.0
species: 443074

464596
type: SpeciesReference
stoichiometry: 1.0
species: 442174

446093
type: Reaction
kinetic law: 468884
product: 468871
product: 468858
reactant: 468846
fast: false
reversible: false

468884
type: KineticLaw
local parameters: 353099
notes: k3*Ras_slash_GAP_slash_GAP_minus_inact_minus_ras_slash_GAP_minus_inact_minus_ras_cplx

353099
type: LocalParameter
units: 462030
value: 1.5E-14

468871
type: SpeciesReference
stoichiometry: 1.0
species: 441194

441194
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.01
initial amount: NaN
in compartment: 439494

468858
type: SpeciesReference
stoichiometry: 1.0
species: 441154

441154
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 439494

468846
type: SpeciesReference
stoichiometry: 1.0
species: 441214

442374
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

439618
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 9.43511111111111E-21
initial amount: NaN
in compartment: 439494

444593
type: Reaction
kinetic law: 465247
product: 465235
reactant: 465223
reactant: 465211
fast: false
reversible: true

465247
type: KineticLaw
local parameters: 352942
local parameters: 352941
notes: kf*PKA_slash_R2C2_minus_cAMP2*cAMP-kb*PKA_slash_R2C2_minus_cAMP3

352942
type: LocalParameter
units: 462030
value: 1.65E-13

352941
type: LocalParameter
units: 462115
value: 1.1249955E-13

465235
type: SpeciesReference
stoichiometry: 1.0
species: 442594

442594
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

465223
type: SpeciesReference
stoichiometry: 1.0
species: 442714

465211
type: SpeciesReference
stoichiometry: 1.0
species: 442574

443793
type: Reaction
kinetic law: 463146
product: 463134
product: 463122
reactant: 463110
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

463146
type: KineticLaw
local parameters: 352812
local parameters: 352811
notes: kf*PLCbeta_slash_PLC_minus_Ca_minus_Gq-kb*G_star_GDP*PLCbeta_slash_PLC_minus_Ca

352812
type: LocalParameter
units: 462115
value: 0.0

352811
type: LocalParameter
units: 462030
value: 1.995E-17

463134
type: SpeciesReference
stoichiometry: 1.0
species: 440274

463122
type: SpeciesReference
stoichiometry: 1.0
species: 440414

440414
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

463110
type: SpeciesReference
stoichiometry: 1.0
species: 440314

440794
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

446773
type: Reaction
kinetic law: 470558
product: 470546
product: 470534
reactant: 470522
fast: false
reversible: false

470558
type: KineticLaw
local parameters: 353231
notes: k3*PP1_minus_active_slash_Deph_thr286b_slash_Deph_thr286b_cplx

353231
type: LocalParameter
units: 462030
value: 5.25E-16

470546
type: SpeciesReference
stoichiometry: 1.0
species: 441954

470534
type: SpeciesReference
stoichiometry: 1.0
species: 441754

470522
type: SpeciesReference
stoichiometry: 1.0
species: 442054

443494
type: Reaction
kinetic law: 462310
product: 462298
reactant: 462286
fast: false
reversible: true

462310
type: KineticLaw
local parameters: 352758
local parameters: 352757
notes: kf*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_memb_star_

352758
type: LocalParameter
units: 462030
value: 5.2539E-15

352757
type: LocalParameter
units: 462030
value: 1.90575E-15

462298
type: SpeciesReference
stoichiometry: 1.0
species: 439594

462286
type: SpeciesReference
stoichiometry: 1.0
species: 439534

439714
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 2.51888888888889E-19
initial amount: NaN
in compartment: 439494

444033
type: Reaction
kinetic law: 463967
product: 463954
reactant: 463942
fast: false
reversible: true

463967
type: KineticLaw
local parameters: 352866
local parameters: 352863
notes: kf*Ras_slash_inact_minus_GEF_star_-kb*Ras_slash_inact_minus_GEF

352866
type: LocalParameter
units: 462030
value: 0.0

352863
type: LocalParameter
units: 462030
value: 1.5E-15

463954
type: SpeciesReference
stoichiometry: 1.0
species: 441074

463942
type: SpeciesReference
stoichiometry: 1.0
species: 441234

446033
type: Reaction
kinetic law: 468738
product: 468726
reactant: 468714
reactant: 468702
notes: Kinetics same as GEF-bg-act-ras
fast: false
reversible: true

468738
type: KineticLaw
local parameters: 353092
local parameters: 353091
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

353092
type: LocalParameter
units: 462030
value: 1.2E-16

353091
type: LocalParameter
units: 462115
value: 2.97E-16

468726
type: SpeciesReference
stoichiometry: 1.0
species: 441114

441114
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

468714
type: SpeciesReference
stoichiometry: 1.0
species: 441094

468702
type: SpeciesReference
stoichiometry: 1.0
species: 441154

446633
type: Reaction
kinetic law: 470216
product: 470203
reactant: 470191
reactant: 470179
fast: false
reversible: true

470216
type: KineticLaw
local parameters: 353201
local parameters: 353198
notes: k1*CaMKII_slash_CaMKII_star__star__star_*PP1_minus_active-k2*PP1_minus_active_slash_Deph_minus_thr305_slash_Deph_minus_thr305_cplx

353201
type: LocalParameter
units: 462030
value: 2.1E-15

353198
type: LocalParameter
units: 462115
value: 5.147955E-16

470203
type: SpeciesReference
stoichiometry: 1.0
species: 441994

470191
type: SpeciesReference
stoichiometry: 1.0
species: 441954

470179
type: SpeciesReference
stoichiometry: 1.0
species: 441814

445993
type: Reaction
kinetic law: 468641
product: 468629
reactant: 468617
reactant: 468605
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

468641
type: KineticLaw
local parameters: 353089
local parameters: 353088
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

353089
type: LocalParameter
units: 462030
value: 1.2E-16

353088
type: LocalParameter
units: 462115
value: 2.97E-16

468629
type: SpeciesReference
stoichiometry: 1.0
species: 441054

441054
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

468617
type: SpeciesReference
stoichiometry: 1.0
species: 441034

441034
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

468605
type: SpeciesReference
stoichiometry: 1.0
species: 441154

462176
type: SBMLUnit
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE

446173
type: Reaction
kinetic law: 469076
product: 469064
product: 469052
reactant: 469040
fast: false
reversible: false

469076
type: KineticLaw
local parameters: 353105
notes: k3*PKA_minus_active_slash_PKA_minus_phosph_minus_GEF_slash_PKA_minus_phosph_minus_GEF_cplx

353105
type: LocalParameter
units: 462030
value: 1.35E-14

469064
type: SpeciesReference
stoichiometry: 1.0
species: 441294

469052
type: SpeciesReference
stoichiometry: 1.0
species: 441234

469040
type: SpeciesReference
stoichiometry: 1.0
species: 441314

446213
type: Reaction
kinetic law: 469173
product: 469160
product: 469148
reactant: 469136
fast: false
reversible: false

469173
type: KineticLaw
local parameters: 353111
notes: k3*PKA_minus_active_slash_PKA_minus_phosph_minus_I1_slash_PKA_minus_phosph_minus_I1_cplx

353111
type: LocalParameter
units: 462030
value: 1.35E-14

469160
type: SpeciesReference
stoichiometry: 1.0
species: 441294

469148
type: SpeciesReference
stoichiometry: 1.0
species: 442274

469136
type: SpeciesReference
stoichiometry: 1.0
species: 441334

444613
type: Reaction
kinetic law: 465295
product: 465283
reactant: 465271
reactant: 465259
fast: false
reversible: true

465295
type: KineticLaw
local parameters: 352946
local parameters: 352943
notes: kf*cAMP*PKA_slash_R2C2_minus_cAMP3-kb*PKA_slash_R2C2_minus_cAMP4

352946
type: LocalParameter
units: 462030
value: 4.875E-14

352943
type: LocalParameter
units: 462115
value: 1.1249955E-13

465283
type: SpeciesReference
stoichiometry: 1.0
species: 442614

465271
type: SpeciesReference
stoichiometry: 1.0
species: 442594

465259
type: SpeciesReference
stoichiometry: 1.0
species: 442714

443454
type: Reaction
kinetic law: 462224
product: 462212
reactant: 462200
reactant: 462188
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

462224
type: KineticLaw
local parameters: 352754
local parameters: 352753
notes: kf*PKC_slash_PKC_minus_cytosolic*Ca-kb*PKC_slash_PKC_minus_Ca

352754
type: LocalParameter
units: 462030
value: 7.5E-16

352753
type: LocalParameter
units: 462115
value: 9.000045E-16

462212
type: SpeciesReference
stoichiometry: 1.0
species: 439534

462200
type: SpeciesReference
stoichiometry: 1.0
species: 443074

462188
type: SpeciesReference
stoichiometry: 1.0
species: 439734

443514
type: Reaction
kinetic law: 462347
product: 462335
reactant: 462322
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

462347
type: KineticLaw
local parameters: 352760
local parameters: 352759
notes: kf*PKC_slash_PKC_minus_Ca_minus_DAG-kb*PKC_slash_PKC_minus_DAG_minus_memb_star_

352760
type: LocalParameter
units: 462030
value: 1.5E-16

352759
type: LocalParameter
units: 462030
value: 1.5E-15

462335
type: SpeciesReference
stoichiometry: 1.0
species: 439618

462322
type: SpeciesReference
stoichiometry: 1.0
species: 439674

444913
type: Reaction
kinetic law: 465983
product: 465971
reactant: 465959
reactant: 465947
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

465983
type: KineticLaw
local parameters: 352981
local parameters: 352980
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

352981
type: LocalParameter
units: 462030
value: 2.4E-14

352980
type: LocalParameter
units: 462115
value: 9.000045E-15

465971
type: SpeciesReference
stoichiometry: 1.0
species: 439814

465959
type: SpeciesReference
stoichiometry: 1.0
species: 443294

465947
type: SpeciesReference
stoichiometry: 1.0
species: 441194

446493
type: Reaction
kinetic law: 469877
product: 469865
product: 469853
reactant: 469840
fast: false
reversible: false

469877
type: KineticLaw
local parameters: 353168
notes: k3*CaMKII_slash_tot_CaM_CaMKII_slash_CaM_act_286_slash_CaM_act_286_cplx

353168
type: LocalParameter
units: 462030
value: 7.5E-16

469865
type: SpeciesReference
stoichiometry: 1.0
species: 443314

469853
type: SpeciesReference
stoichiometry: 1.0
species: 441794

469840
type: SpeciesReference
stoichiometry: 1.0
species: 441894

446073
type: Reaction
kinetic law: 468834
product: 468822
reactant: 468810
reactant: 468798
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

468834
type: KineticLaw
local parameters: 353098
local parameters: 353095
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

353098
type: LocalParameter
units: 462030
value: 6.0E-14

353095
type: LocalParameter
units: 462115
value: 7.42284E-14

468822
type: SpeciesReference
stoichiometry: 1.0
species: 441214

468810
type: SpeciesReference
stoichiometry: 1.0
species: 441194

468798
type: SpeciesReference
stoichiometry: 1.0
species: 441134

442674
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.25
initial amount: NaN
in compartment: 439494

443854
type: Reaction
kinetic law: 463472
product: 463460
reactant: 463448
reactant: 463436
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

463472
type: KineticLaw
local parameters: 352832
local parameters: 352831
notes: kf*Gq_slash_G_minus_GDP*Gq_slash_Rec_minus_Glu-kb*Gq_slash_Rec_minus_Glu_minus_Gq

352832
type: LocalParameter
units: 462030
value: 1.5E-19

352831
type: LocalParameter
units: 462115
value: 9.000045E-18

463460
type: SpeciesReference
stoichiometry: 1.0
species: 440514

463448
type: SpeciesReference
stoichiometry: 1.0
species: 440474

463436
type: SpeciesReference
stoichiometry: 1.0
species: 440434

440434
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 439494

444153
type: Reaction
kinetic law: 464219
product: 464207
reactant: 464195
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

464219
type: KineticLaw
local parameters: 352882
local parameters: 352881
notes: kf*Sos_slash_Sos_star_-kb*Sos_slash_Sos

352882
type: LocalParameter
units: 462030
value: 0.0

352881
type: LocalParameter
units: 462030
value: 1.5E-18

464207
type: SpeciesReference
stoichiometry: 1.0
species: 441654

464195
type: SpeciesReference
stoichiometry: 1.0
species: 441634

445493
type: Reaction
kinetic law: 467434
product: 467422
product: 467409
product: 467396
reactant: 467383
fast: false
reversible: false

467434
type: KineticLaw
local parameters: 353039
notes: k3*PLCbeta_slash_PLC_minus_Ca_minus_Gq_slash_PLCb_minus_Ca_minus_Gq_slash_PLCb_minus_Ca_minus_Gq_cplx

353039
type: LocalParameter
units: 462030
value: 7.2E-14

467422
type: SpeciesReference
stoichiometry: 1.0
species: 440314

467409
type: SpeciesReference
stoichiometry: 1.0
species: 440234

440234
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.73
initial amount: NaN
in compartment: 439494

467396
type: SpeciesReference
stoichiometry: 1.0
species: 439754

467383
type: SpeciesReference
stoichiometry: 1.0
species: 440334

440334
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

446753
type: Reaction
kinetic law: 470509
product: 470496
reactant: 470484
reactant: 470472
fast: false
reversible: true

470509
type: KineticLaw
local parameters: 353228
local parameters: 353225
notes: k1*CaMKII_slash_CaMKII_minus_thr286*PP1_minus_active-k2*PP1_minus_active_slash_Deph_thr286b_slash_Deph_thr286b_cplx

353228
type: LocalParameter
units: 462030
value: 2.1E-15

353225
type: LocalParameter
units: 462115
value: 5.147955E-16

470496
type: SpeciesReference
stoichiometry: 1.0
species: 442054

470484
type: SpeciesReference
stoichiometry: 1.0
species: 441954

470472
type: SpeciesReference
stoichiometry: 1.0
species: 441834

443554
type: Reaction
kinetic law: 462432
product: 462420
reactant: 462408
notes: Assume slowish too. Schaechter and Benowitz
fast: false
reversible: true

462432
type: KineticLaw
local parameters: 352766
local parameters: 352765
notes: kf*PKC_slash_PKC_minus_DAG_minus_AA-kb*PKC_slash_PKC_minus_DAG_minus_AA_star_

352766
type: LocalParameter
units: 462030
value: 3.0E-16

352765
type: LocalParameter
units: 462030
value: 3.0E-15

462420
type: SpeciesReference
stoichiometry: 1.0
species: 439554

462408
type: SpeciesReference
stoichiometry: 1.0
species: 439714

445273
type: Reaction
kinetic law: 466864
product: 466852
reactant: 466840
reactant: 466828
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

466864
type: KineticLaw
local parameters: 353017
local parameters: 353016
notes: k1*PLA2_slash_APC*PLA2_slash_PLA2_star__minus_Ca-k2*PLA2_slash_PLA2_star__minus_Ca_slash_kenz_slash_kenz_cplx

353017
type: LocalParameter
units: 462030
value: 7.2E-13

353016
type: LocalParameter
units: 462115
value: 4.499955E-14

466852
type: SpeciesReference
stoichiometry: 1.0
species: 440114

466840
type: SpeciesReference
stoichiometry: 1.0
species: 440094

466828
type: SpeciesReference
stoichiometry: 1.0
species: 443114

443834
type: Reaction
kinetic law: 463388
product: 463376
reactant: 463364
reactant: 463351
notes: kf == kg3 = 1e-5 /cell/sec. As usual, there is no back-reaction kb = 0
fast: false
reversible: true

463388
type: KineticLaw
local parameters: 352826
local parameters: 352825
notes: kf*G_star_GDP*BetaGamma-kb*Gq_slash_G_minus_GDP

352826
type: LocalParameter
units: 462030
value: 0.0

352825
type: LocalParameter
units: 462115
value: 9.000045E-15

463376
type: SpeciesReference
stoichiometry: 1.0
species: 440434

463364
type: SpeciesReference
stoichiometry: 1.0
species: 440374

463351
type: SpeciesReference
stoichiometry: 1.0
species: 440414

446253
type: Reaction
kinetic law: 469271
product: 469259
product: 469247
reactant: 469235
fast: false
reversible: false

469271
type: KineticLaw
local parameters: 353115
notes: k3*PKA_minus_active_slash_phosph_minus_PDE_slash_phosph_minus_PDE_cplx

353115
type: LocalParameter
units: 462030
value: 1.35E-14

469259
type: SpeciesReference
stoichiometry: 1.0
species: 441294

469247
type: SpeciesReference
stoichiometry: 1.0
species: 442934

442934
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

469235
type: SpeciesReference
stoichiometry: 1.0
species: 441354

446333
type: Reaction
kinetic law: 469465
product: 469453
product: 469441
reactant: 469429
fast: false
reversible: false

469465
type: KineticLaw
local parameters: 353131
notes: k3*EGFR_slash_L_dot_EGFR_slash_phosph_PLC_g_slash_phosph_PLC_g_cplx

353131
type: LocalParameter
units: 462030
value: 3.0E-16

469453
type: SpeciesReference
stoichiometry: 1.0
species: 441454

469441
type: SpeciesReference
stoichiometry: 1.0
species: 441734

469429
type: SpeciesReference
stoichiometry: 1.0
species: 441474

441474
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

444733
type: Reaction
kinetic law: 465572
product: 465560
reactant: 465548
reactant: 465536
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

465572
type: KineticLaw
local parameters: 352964
local parameters: 352961
notes: kf*AC_slash_AC2*Gs_minus_alpha-kb*AC_slash_AC2_minus_Gs

352964
type: LocalParameter
units: 462030
value: 1.5E-15

352961
type: LocalParameter
units: 462115
value: 7.499925E-13

465560
type: SpeciesReference
stoichiometry: 1.0
species: 442794

465548
type: SpeciesReference
stoichiometry: 1.0
species: 443054

465536
type: SpeciesReference
stoichiometry: 1.0
species: 442814

446393
type: Reaction
reversible: false
modifier: 469611
fast: false
kinetic law: 469623
product: 469598
reactant: 469574
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.
product: 469586

469623
type: KineticLaw
local parameters: 353144
local parameters: 353141
notes: kcat*PLC_g_slash_Ca_dot_PLC_g*PIP2/(Km+PIP2)

353144
type: LocalParameter
units: 461994
value: 97.2222222222222

353141
type: LocalParameter
units: 462030
value: 2.1E-14

469598
type: SpeciesReference
stoichiometry: 1.0
species: 440234

469574
type: SpeciesReference
stoichiometry: 1.0
species: 443214

469586
type: SpeciesReference
stoichiometry: 1.0
species: 439754

443574
type: Reaction
kinetic law: 462469
product: 462457
reactant: 462445
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

462469
type: KineticLaw
local parameters: 352770
local parameters: 352767
notes: kf*PKC_slash_PKC_minus_cytosolic-kb*PKC_slash_PKC_minus_basal_star_

352770
type: LocalParameter
units: 462030
value: 7.5E-14

352767
type: LocalParameter
units: 462030
value: 1.5E-15

462457
type: SpeciesReference
stoichiometry: 1.0
species: 439634

462445
type: SpeciesReference
stoichiometry: 1.0
species: 439734

440454
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.3
initial amount: NaN
in compartment: 439494

439483
type: Compartment
constant: true
size: 1.0E-18
spatial dimensions: 3.0

440634
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

446433
type: Reaction
kinetic law: 469731
product: 469719
reactant: 469707
reactant: 469695
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

469731
type: KineticLaw
local parameters: 353156
local parameters: 353153
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

353156
type: LocalParameter
units: 462030
value: 3.6E-14

353153
type: LocalParameter
units: 462115
value: 3.961305E-16

469719
type: SpeciesReference
stoichiometry: 1.0
species: 441874

441874
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

469707
type: SpeciesReference
stoichiometry: 1.0
species: 443314

469695
type: SpeciesReference
stoichiometry: 1.0
species: 441834

443614
type: Reaction
kinetic law: 462567
product: 462555
reactant: 462542
reactant: 462530
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

462567
type: KineticLaw
local parameters: 352776
local parameters: 352773
notes: kf*PKC_slash_PKC_minus_cytosolic*DAG-kb*PKC_slash_PKC_minus_DAG

352776
type: LocalParameter
units: 462030
value: 1.5E-16

352773
type: LocalParameter
units: 462115
value: 9.000045E-19

462555
type: SpeciesReference
stoichiometry: 1.0
species: 439694

462542
type: SpeciesReference
stoichiometry: 1.0
species: 439754

462530
type: SpeciesReference
stoichiometry: 1.0
species: 439734

443734
type: Reaction
kinetic law: 462929
product: 462917
reactant: 462905
fast: false
reversible: true

462929
type: KineticLaw
local parameters: 352798
local parameters: 352797
notes: kf*PLA2_slash_PLA2_star_-kb*PLA2_slash_PLA2_minus_cytosolic

352798
type: LocalParameter
units: 462030
value: 0.0

352797
type: LocalParameter
units: 462030
value: 2.55E-16

462917
type: SpeciesReference
stoichiometry: 1.0
species: 439914

462905
type: SpeciesReference
stoichiometry: 1.0
species: 440134

446113
type: Reaction
kinetic law: 468932
product: 468920
reactant: 468908
reactant: 468896
notes: Kinetics same as GEF-bg_act-ras
fast: false
reversible: true

468932
type: KineticLaw
local parameters: 353101
local parameters: 353100
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

353101
type: LocalParameter
units: 462030
value: 1.2E-16

353100
type: LocalParameter
units: 462115
value: 2.97E-16

468920
type: SpeciesReference
stoichiometry: 1.0
species: 441274

441274
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

468908
type: SpeciesReference
stoichiometry: 1.0
species: 441254

468896
type: SpeciesReference
stoichiometry: 1.0
species: 441154

446513
type: Reaction
kinetic law: 469926
product: 469914
reactant: 469901
reactant: 469889
notes: See Hanson and Schulman again, for afterburst rates of phosph.
fast: false
reversible: true

469926
type: KineticLaw
local parameters: 353174
local parameters: 353171
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

353174
type: LocalParameter
units: 462030
value: 3.6E-14

353171
type: LocalParameter
units: 462115
value: 2.571345E-16

469914
type: SpeciesReference
stoichiometry: 1.0
species: 441914

469901
type: SpeciesReference
stoichiometry: 1.0
species: 443334

469889
type: SpeciesReference
stoichiometry: 1.0
species: 441834

446613
type: Reaction
kinetic law: 470167
product: 470155
product: 470142
reactant: 470130
fast: false
reversible: false

470167
type: KineticLaw
local parameters: 353195
notes: k3*PP1_minus_active_slash_Deph_minus_thr286_slash_Deph_minus_thr286_cplx

353195
type: LocalParameter
units: 462030
value: 5.25E-16

470155
type: SpeciesReference
stoichiometry: 1.0
species: 441954

470142
type: SpeciesReference
stoichiometry: 1.0
species: 441774

470130
type: SpeciesReference
stoichiometry: 1.0
species: 441974

440074
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

443973
type: Reaction
kinetic law: 463845
product: 463833
reactant: 463821
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

463845
type: KineticLaw
local parameters: 352856
local parameters: 352855
notes: kf*Ras_slash_GTP_minus_Ras-kb*Ras_slash_GDP_minus_Ras

352856
type: LocalParameter
units: 462030
value: 0.0

352855
type: LocalParameter
units: 462030
value: 1.5E-19

463833
type: SpeciesReference
stoichiometry: 1.0
species: 441154

463821
type: SpeciesReference
stoichiometry: 1.0
species: 441134

446453
type: Reaction
kinetic law: 469779
product: 469767
product: 469755
reactant: 469743
fast: false
reversible: false

469779
type: KineticLaw
local parameters: 353159
notes: k3*CaMKII_slash_tot_CaM_CaMKII_slash_CaM_act_305_slash_CaM_act_305_cplx

353159
type: LocalParameter
units: 462030
value: 9.0E-15

469767
type: SpeciesReference
stoichiometry: 1.0
species: 443314

469755
type: SpeciesReference
stoichiometry: 1.0
species: 441814

469743
type: SpeciesReference
stoichiometry: 1.0
species: 441874

446833
type: Reaction
kinetic law: 470704
product: 470692
reactant: 470680
reactant: 470668
fast: false
reversible: true

470704
type: KineticLaw
local parameters: 353246
local parameters: 353243
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

353246
type: LocalParameter
units: 462030
value: 2.04E-15

353243
type: LocalParameter
units: 462115
value: 5.13E-16

470692
type: SpeciesReference
stoichiometry: 1.0
species: 442214

442214
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

470680
type: SpeciesReference
stoichiometry: 1.0
species: 443354

470668
type: SpeciesReference
stoichiometry: 1.0
species: 442274

445873
type: Reaction
kinetic law: 468353
product: 468341
reactant: 468329
reactant: 468317
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

353077
type: LocalParameter
units: 462030
value: 3.6E-14

353076
type: LocalParameter
units: 462115
value: 2.87415E-15

468341
type: SpeciesReference
stoichiometry: 1.0
species: 440974

468329
type: SpeciesReference
stoichiometry: 1.0
species: 440934

468317
type: SpeciesReference
stoichiometry: 1.0
species: 440674

446553
type: Reaction
kinetic law: 470022
product: 470010
reactant: 469998
reactant: 469986
fast: false
reversible: true

470022
type: KineticLaw
local parameters: 353183
local parameters: 353180
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

353183
type: LocalParameter
units: 462030
value: 3.0E-15

353180
type: LocalParameter
units: 462115
value: 2.142855E-17

470010
type: SpeciesReference
stoichiometry: 1.0
species: 441934

441934
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

469998
type: SpeciesReference
stoichiometry: 1.0
species: 443334

469986
type: SpeciesReference
stoichiometry: 1.0
species: 441774

446133
type: Reaction
kinetic law: 468980
product: 468968
product: 468956
reactant: 468944
fast: false
reversible: false

468980
type: KineticLaw
local parameters: 353102
notes: k3*Ras_slash_CaM_minus_GEF_slash_CaM_minus_GEF_minus_act_minus_ras_slash_CaM_minus_GEF_minus_act_minus_ras_cplx

353102
type: LocalParameter
units: 462030
value: 3.0E-17

468968
type: SpeciesReference
stoichiometry: 1.0
species: 441254

468956
type: SpeciesReference
stoichiometry: 1.0
species: 441134

468944
type: SpeciesReference
stoichiometry: 1.0
species: 441274

444113
type: Reaction
kinetic law: 464135
product: 464123
reactant: 464111
reactant: 464099
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

464135
type: KineticLaw
local parameters: 352876
local parameters: 352875
notes: kf*Sos_slash_Sos_dot_Grb2*EGFR_slash_SHC_star_-kb*Shc_star__dot_Sos_dot_Grb2

352876
type: LocalParameter
units: 462030
value: 1.5E-16

352875
type: LocalParameter
units: 462115
value: 7.499655E-16

464123
type: SpeciesReference
stoichiometry: 1.0
species: 441394

464111
type: SpeciesReference
stoichiometry: 1.0
species: 441534

464099
type: SpeciesReference
stoichiometry: 1.0
species: 441614

443873
type: Reaction
kinetic law: 463520
product: 463508
reactant: 463496
reactant: 463484
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

463520
type: KineticLaw
local parameters: 352836
local parameters: 352833
notes: kf*Glu*Gq_slash_Rec_minus_Gq-kb*Gq_slash_Rec_minus_Glu_minus_Gq

352836
type: LocalParameter
units: 462030
value: 1.5E-16

352833
type: LocalParameter
units: 462115
value: 2.520045E-14

463508
type: SpeciesReference
stoichiometry: 1.0
species: 440514

463496
type: SpeciesReference
stoichiometry: 1.0
species: 440494

463484
type: SpeciesReference
stoichiometry: 1.0
species: 443154

443154
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: 439494

445453
type: Reaction
kinetic law: 467318
product: 467305
product: 467292
product: 467279
reactant: 467267
fast: false
reversible: false

467318
type: KineticLaw
local parameters: 353033
notes: k3*PLCbeta_slash_PLC_minus_Ca_slash_PLC_minus_Ca_slash_PLC_minus_Ca_cplx

353033
type: LocalParameter
units: 462030
value: 1.5E-14

467305
type: SpeciesReference
stoichiometry: 1.0
species: 440274

467292
type: SpeciesReference
stoichiometry: 1.0
species: 440234

467279
type: SpeciesReference
stoichiometry: 1.0
species: 439754

467267
type: SpeciesReference
stoichiometry: 1.0
species: 440294

440294
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

443893
type: Reaction
kinetic law: 463629
product: 463617
reactant: 463605
reactant: 463593
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

463629
type: KineticLaw
local parameters: 352842
local parameters: 352839
notes: kf*Gq_slash_G_minus_GDP*Gq_slash_mGluR-kb*Gq_slash_Rec_minus_Gq

352842
type: LocalParameter
units: 462030
value: 1.5E-15

352839
type: LocalParameter
units: 462115
value: 9.000045E-16

463617
type: SpeciesReference
stoichiometry: 1.0
species: 440494

463605
type: SpeciesReference
stoichiometry: 1.0
species: 440454

463593
type: SpeciesReference
stoichiometry: 1.0
species: 440434

446733
type: Reaction
kinetic law: 470460
product: 470447
product: 470435
reactant: 470423
fast: false
reversible: false

470460
type: KineticLaw
local parameters: 353222
notes: k3*PP1_minus_active_slash_Deph_minus_thr286c_slash_Deph_minus_thr286c_cplx

353222
type: LocalParameter
units: 462030
value: 5.25E-16

470447
type: SpeciesReference
stoichiometry: 1.0
species: 441954

470435
type: SpeciesReference
stoichiometry: 1.0
species: 441854

441854
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

470423
type: SpeciesReference
stoichiometry: 1.0
species: 442034

446413
type: Reaction
product: 469659
fast: false
product: 469647
reversible: false
modifier: 469671
reactant: 469635
kinetic law: 469683
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.

469659
type: SpeciesReference
stoichiometry: 1.0
species: 440234

469647
type: SpeciesReference
stoichiometry: 1.0
species: 439754

469635
type: SpeciesReference
stoichiometry: 1.0
species: 443214

469683
type: KineticLaw
local parameters: 353150
local parameters: 353147
notes: kcat*PLC_g_slash_Ca_dot_PLC_g_star_*PIP2/(Km+PIP2)

353150
type: LocalParameter
units: 461994
value: 19.7916666666667

353147
type: LocalParameter
units: 462030
value: 8.55E-14

445773
type: Reaction
kinetic law: 468111
product: 468099
product: 468087
reactant: 468075
fast: false
reversible: false

468111
type: KineticLaw
local parameters: 353066
notes: k3*MKP_minus_1_slash_MKP1_minus_tyr_minus_deph_slash_MKP1_minus_tyr_minus_deph_cplx

353066
type: LocalParameter
units: 462030
value: 6.0E-15

468099
type: SpeciesReference
stoichiometry: 1.0
species: 440874

468087
type: SpeciesReference
stoichiometry: 1.0
species: 440614

468075
type: SpeciesReference
stoichiometry: 1.0
species: 440894

445633
type: Reaction
kinetic law: 467772
product: 467760
reactant: 467748
reactant: 467736
notes: Kinetics are the same as for the craf_1* activity, ie., k1=5.5e-6, k2=0.42, k3 = 0.105 These are basedo n Force et al PNAS USA 91 1270-1274, 1994., but k1 is scaled up 5x (ie., Km is scaled down 5x to the value used here and for craf_1* activity: Km = 0.1591).
fast: false
reversible: true

467772
type: KineticLaw
local parameters: 353053
local parameters: 353052
notes: k1*MAPK_slash_MAPKK_minus_ser*MAPK_slash_Raf_minus_GTP_minus_Ras-k2*MAPK_slash_Raf_minus_GTP_minus_Ras_slash_Raf_minus_GTP_minus_Ras_dot_2_slash_Raf_minus_GTP_minus_Ras_dot_2_cplx

353053
type: LocalParameter
units: 462030
value: 1.8E-15

353052
type: LocalParameter
units: 462115
value: 1.41426E-14

467760
type: SpeciesReference
stoichiometry: 1.0
species: 440794

467748
type: SpeciesReference
stoichiometry: 1.0
species: 440754

467736
type: SpeciesReference
stoichiometry: 1.0
species: 440734

445093
type: Reaction
kinetic law: 466428
product: 466416
product: 466404
reactant: 466392
fast: false
reversible: false

466428
type: KineticLaw
local parameters: 352997
notes: k3*PKC_minus_active_slash_phosph_minus_AC2_slash_phosph_minus_AC2_cplx

352997
type: LocalParameter
units: 462030
value: 6.0E-15

466416
type: SpeciesReference
stoichiometry: 1.0
species: 443294

466404
type: SpeciesReference
stoichiometry: 1.0
species: 442774

466392
type: SpeciesReference
stoichiometry: 1.0
species: 439894

446573
type: Reaction
kinetic law: 470070
product: 470058
product: 470046
reactant: 470034
fast: false
reversible: false

470070
type: KineticLaw
local parameters: 353186
notes: k3*CaMKII_slash_tot_autonomous_CaMKII_slash_auton_286_slash_auton_286_cplx

353186
type: LocalParameter
units: 462030
value: 7.5E-16

470058
type: SpeciesReference
stoichiometry: 1.0
species: 443334

470046
type: SpeciesReference
stoichiometry: 1.0
species: 441794

470034
type: SpeciesReference
stoichiometry: 1.0
species: 441934

446953
type: Reaction
kinetic law: 470996
product: 470983
reactant: 470971
reactant: 470958
notes: k1 changed from 3.3e-6 to 6.6e-6
fast: false
reversible: true

470996
type: KineticLaw
local parameters: 353273
local parameters: 353270
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

353273
type: LocalParameter
units: 462030
value: 3.75E-14

353270
type: LocalParameter
units: 462115
value: 5.94E-15

470983
type: SpeciesReference
stoichiometry: 1.0
species: 442374

470971
type: SpeciesReference
stoichiometry: 1.0
species: 442334

470958
type: SpeciesReference
stoichiometry: 1.0
species: 442294

445193
type: Reaction
kinetic law: 466672
product: 466660
reactant: 466648
reactant: 466636
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

466672
type: KineticLaw
local parameters: 353008
local parameters: 353007
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

353008
type: LocalParameter
units: 462030
value: 2.16E-13

353007
type: LocalParameter
units: 462115
value: 1.35E-14

466660
type: SpeciesReference
stoichiometry: 1.0
species: 440034

466648
type: SpeciesReference
stoichiometry: 1.0
species: 440014

466636
type: SpeciesReference
stoichiometry: 1.0
species: 443114

446673
type: Reaction
kinetic law: 470313
product: 470301
reactant: 470289
reactant: 470277
notes: See Cohen et al
fast: false
reversible: true

470313
type: KineticLaw
local parameters: 353210
local parameters: 353207
notes: k1*CaMKII_slash_CaMK_minus_thr306*PP1_minus_active-k2*PP1_minus_active_slash_Deph_minus_thr306_slash_Deph_minus_thr306_cplx

353210
type: LocalParameter
units: 462030
value: 2.1E-15

353207
type: LocalParameter
units: 462115
value: 5.147955E-16

470301
type: SpeciesReference
stoichiometry: 1.0
species: 442014

470289
type: SpeciesReference
stoichiometry: 1.0
species: 441954

470277
type: SpeciesReference
stoichiometry: 1.0
species: 441854

443714
type: Reaction
kinetic law: 462893
product: 462881
reactant: 462869
reactant: 462857
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

462893
type: KineticLaw
local parameters: 352796
local parameters: 352793
notes: kf*PLA2_slash_PLA2_star_*Ca-kb*PLA2_slash_PLA2_star__minus_Ca

352796
type: LocalParameter
units: 462030
value: 1.5E-16

352793
type: LocalParameter
units: 462115
value: 9.000045E-15

462881
type: SpeciesReference
stoichiometry: 1.0
species: 440094

462869
type: SpeciesReference
stoichiometry: 1.0
species: 443074

462857
type: SpeciesReference
stoichiometry: 1.0
species: 440134

446353
type: Reaction
kinetic law: 469514
product: 469502
reactant: 469489
reactant: 469477
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

469514
type: KineticLaw
local parameters: 353137
local parameters: 353134
notes: k1*EGFR_slash_SHC*EGFR_slash_L_dot_EGFR-k2*EGFR_slash_L_dot_EGFR_slash_phosph_Shc_slash_phosph_Shc_cplx

353137
type: LocalParameter
units: 462030
value: 1.2E-15

353134
type: LocalParameter
units: 462115
value: 1.799955E-15

469502
type: SpeciesReference
stoichiometry: 1.0
species: 441494

469489
type: SpeciesReference
stoichiometry: 1.0
species: 441454

469477
type: SpeciesReference
stoichiometry: 1.0
species: 441514

444953
type: Reaction
kinetic law: 466079
product: 466067
reactant: 466055
reactant: 466043
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

466079
type: KineticLaw
local parameters: 352984
local parameters: 352983
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

352984
type: LocalParameter
units: 462030
value: 2.4E-14

352983
type: LocalParameter
units: 462115
value: 9.000045E-15

466067
type: SpeciesReference
stoichiometry: 1.0
species: 439834

466055
type: SpeciesReference
stoichiometry: 1.0
species: 443294

466043
type: SpeciesReference
stoichiometry: 1.0
species: 441074

443953
type: Reaction
kinetic law: 463809
product: 463797
reactant: 463785
fast: false
reversible: true

463809
type: KineticLaw
local parameters: 352854
local parameters: 352851
notes: kf*Ras_slash_GEF_star_-kb*Ras_slash_inact_minus_GEF

352854
type: LocalParameter
units: 462030
value: 0.0

352851
type: LocalParameter
units: 462030
value: 1.5E-15

463797
type: SpeciesReference
stoichiometry: 1.0
species: 441074

463785
type: SpeciesReference
stoichiometry: 1.0
species: 441094

445673
type: Reaction
kinetic law: 467870
product: 467858
reactant: 467846
reactant: 467834
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

467870
type: KineticLaw
local parameters: 353056
local parameters: 353055
notes: k1*MAPK_slash_MAPKK*MAPK_slash_Raf_star__minus_GTP_minus_Ras-k2*MAPK_slash_Raf_star__minus_GTP_minus_Ras_slash_Raf_star__minus_GTP_minus_Ras_dot_1_slash_Raf_star__minus_GTP_minus_Ras_dot_1_cplx

353056
type: LocalParameter
units: 462030
value: 1.8E-15

353055
type: LocalParameter
units: 462115
value: 1.41426E-14

467858
type: SpeciesReference
stoichiometry: 1.0
species: 440834

467846
type: SpeciesReference
stoichiometry: 1.0
species: 440814

467834
type: SpeciesReference
stoichiometry: 1.0
species: 440594

446893
type: Reaction
kinetic law: 470848
product: 470836
product: 470824
reactant: 470812
fast: false
reversible: false

470848
type: KineticLaw
local parameters: 353258
notes: k3*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_minus_PP1_minus_I_star__slash_dephosph_minus_PP1_minus_I_star__cplx

353258
type: LocalParameter
units: 462030
value: 5.1E-16

470836
type: SpeciesReference
stoichiometry: 1.0
species: 443354

470824
type: SpeciesReference
stoichiometry: 1.0
species: 442314

470812
type: SpeciesReference
stoichiometry: 1.0
species: 442234

446993
type: Reaction
kinetic law: 471092
product: 471080
reactant: 471068
reactant: 471056
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

471092
type: KineticLaw
local parameters: 353282
local parameters: 353279
notes: k1*PP1_slash_I1_star_*CaNAB_minus_Ca4-k2*CaNAB_minus_Ca4_slash_dephosph_inhib1_noCaM_slash_dephosph_inhib1_noCaM_cplx

353282
type: LocalParameter
units: 462030
value: 2.04E-16

353279
type: LocalParameter
units: 462115
value: 5.13E-17

471080
type: SpeciesReference
stoichiometry: 1.0
species: 442414

471068
type: SpeciesReference
stoichiometry: 1.0
species: 442394

471056
type: SpeciesReference
stoichiometry: 1.0
species: 442274

445433
type: Reaction
kinetic law: 467254
product: 467242
reactant: 467229
reactant: 467217
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

467254
type: KineticLaw
local parameters: 353032
local parameters: 353031
notes: k1*PIP2*PLCbeta_slash_PLC_minus_Ca-k2*PLCbeta_slash_PLC_minus_Ca_slash_PLC_minus_Ca_slash_PLC_minus_Ca_cplx

353032
type: LocalParameter
units: 462030
value: 6.0E-14

353031
type: LocalParameter
units: 462115
value: 3.78E-15

467242
type: SpeciesReference
stoichiometry: 1.0
species: 440294

467229
type: SpeciesReference
stoichiometry: 1.0
species: 440274

467217
type: SpeciesReference
stoichiometry: 1.0
species: 443214

444513
type: Reaction
kinetic law: 465054
product: 465042
reactant: 465030
reactant: 465018
fast: false
reversible: true

465054
type: KineticLaw
local parameters: 352932
local parameters: 352931
notes: kf*CaM_minus_Ca3*CaNAB_minus_Ca4-kb*PP2B_slash_CaMCa3_minus_CaNAB

352932
type: LocalParameter
units: 462030
value: 1.5E-15

352931
type: LocalParameter
units: 462115
value: 3.357045E-15

465042
type: SpeciesReference
stoichiometry: 1.0
species: 442474

442474
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

465030
type: SpeciesReference
stoichiometry: 1.0
species: 442394

465018
type: SpeciesReference
stoichiometry: 1.0
species: 442154

445853
type: Reaction
kinetic law: 468305
product: 468293
product: 468281
reactant: 468268
fast: false
reversible: false

353075
type: LocalParameter
units: 462030
value: 9.0E-15

468293
type: SpeciesReference
stoichiometry: 1.0
species: 440934

468281
type: SpeciesReference
stoichiometry: 1.0
species: 440554

468268
type: SpeciesReference
stoichiometry: 1.0
species: 440954

446273
type: Reaction
kinetic law: 469319
product: 469307
reactant: 469295
reactant: 469283
fast: false
reversible: true

469319
type: KineticLaw
local parameters: 353119
local parameters: 353116
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

353119
type: LocalParameter
units: 462030
value: 1.2E-16

353116
type: LocalParameter
units: 462115
value: 2.97E-16

469307
type: SpeciesReference
stoichiometry: 1.0
species: 441414

469295
type: SpeciesReference
stoichiometry: 1.0
species: 441394

469283
type: SpeciesReference
stoichiometry: 1.0
species: 441154

443713
type: Reaction
kinetic law: 462845
product: 462833
reactant: 462821
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

462845
type: KineticLaw
local parameters: 352792
local parameters: 352791
notes: kf*AA-kb*PLA2_slash_APC

352792
type: LocalParameter
units: 462030
value: 0.0

352791
type: LocalParameter
units: 462030
value: 6.0E-16

462833
type: SpeciesReference
stoichiometry: 1.0
species: 443114

462821
type: SpeciesReference
stoichiometry: 1.0
species: 439774

446793
type: Reaction
kinetic law: 470607
product: 470594
reactant: 470582
reactant: 470570
notes: From Seki et al ABB 316(2):673-679
fast: false
reversible: true

470607
type: KineticLaw
local parameters: 353237
local parameters: 353234
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

353237
type: LocalParameter
units: 462030
value: 4.005E-15

353234
type: LocalParameter
units: 462115
value: 5.004045E-16

470594
type: SpeciesReference
stoichiometry: 1.0
species: 442194

470582
type: SpeciesReference
stoichiometry: 1.0
species: 443354

470570
type: SpeciesReference
stoichiometry: 1.0
species: 442114

443914
type: Reaction
kinetic law: 463725
product: 463713
reactant: 463701
reactant: 463689
notes: Assume the binding is fast and limited only by the amount of Ras* available. So kf=kb/[craf-1] If kb is 1/sec, then kf = 1/0.2 uM = 1/(0.2 * 6e5) = 8.3e-6 Later: Raise it by 10 X to 4e-5 From Hallberg et al JBC 269:6 3913-3916 1994, 3% of cellular Raf is complexed with Ras. So we raise kb 4x to 4 This step needed to memb-anchor and activate Raf: Leevers et al Nature 369 411-414 May 16, 2003 Changed Ras and Raf to synaptic levels, an increase of about 2x for each. To maintain the percentage of complexed Raf, reduced the kf by 2.4 fold to 10.
fast: false
reversible: true

463725
type: KineticLaw
local parameters: 352848
local parameters: 352845
notes: kf*MAPK_slash_craf_minus_1_star_*Ras_slash_GTP_minus_Ras-kb*MAPK_slash_Raf_star__minus_GTP_minus_Ras

352848
type: LocalParameter
units: 462030
value: 7.5E-16

352845
type: LocalParameter
units: 462115
value: 1.499985E-14

463713
type: SpeciesReference
stoichiometry: 1.0
species: 440814

463701
type: SpeciesReference
stoichiometry: 1.0
species: 441134

463689
type: SpeciesReference
stoichiometry: 1.0
species: 440574

446853
type: Reaction
kinetic law: 470752
product: 470740
product: 470728
reactant: 470716
fast: false
reversible: false

470752
type: KineticLaw
local parameters: 353249
notes: k3*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_inhib1_slash_dephosph_inhib1_cplx

353249
type: LocalParameter
units: 462030
value: 5.1E-16

470740
type: SpeciesReference
stoichiometry: 1.0
species: 443354

470728
type: SpeciesReference
stoichiometry: 1.0
species: 442254

470716
type: SpeciesReference
stoichiometry: 1.0
species: 442214

445693
type: Reaction
kinetic law: 467919
product: 467907
product: 467895
reactant: 467883
fast: false
reversible: false

467919
type: KineticLaw
local parameters: 353057
notes: k3*MAPK_slash_Raf_star__minus_GTP_minus_Ras_slash_Raf_star__minus_GTP_minus_Ras_dot_1_slash_Raf_star__minus_GTP_minus_Ras_dot_1_cplx

353057
type: LocalParameter
units: 462030
value: 4.5E-16

467907
type: SpeciesReference
stoichiometry: 1.0
species: 440814

467895
type: SpeciesReference
stoichiometry: 1.0
species: 440734

467883
type: SpeciesReference
stoichiometry: 1.0
species: 440834

447173
type: Reaction
kinetic law: 471529
product: 471517
reactant: 471505
reactant: 471493
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

471529
type: KineticLaw
local parameters: 353330
local parameters: 353327
notes: k1*cAMP*AC_slash_cAMP_minus_PDE_star_-k2*AC_slash_cAMP_minus_PDE_star__slash_PDE_star__slash_PDE_star__cplx

353330
type: LocalParameter
units: 462030
value: 1.2E-13

353327
type: LocalParameter
units: 462115
value: 7.56E-15

471517
type: SpeciesReference
stoichiometry: 1.0
species: 442954

442954
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

471505
type: SpeciesReference
stoichiometry: 1.0
species: 442934

471493
type: SpeciesReference
stoichiometry: 1.0
species: 442714

447193
type: Reaction
kinetic law: 471577
product: 471565
product: 471553
reactant: 471541
fast: false
reversible: false

471577
type: KineticLaw
local parameters: 353333
notes: k3*AC_slash_cAMP_minus_PDE_star__slash_PDE_star__slash_PDE_star__cplx

353333
type: LocalParameter
units: 462030
value: 3.0E-14

471565
type: SpeciesReference
stoichiometry: 1.0
species: 442934

471553
type: SpeciesReference
stoichiometry: 1.0
species: 442854

471541
type: SpeciesReference
stoichiometry: 1.0
species: 442954

443853
type: Reaction
kinetic law: 463424
product: 463412
reactant: 463400
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

463424
type: KineticLaw
local parameters: 352830
local parameters: 352827
notes: kf*G_star_GTP-kb*G_star_GDP

352830
type: LocalParameter
units: 462030
value: 0.0

352827
type: LocalParameter
units: 462030
value: 1.995E-17

463412
type: SpeciesReference
stoichiometry: 1.0
species: 440414

463400
type: SpeciesReference
stoichiometry: 1.0
species: 440394

445593
type: Reaction
kinetic law: 467676
product: 467664
reactant: 467651
reactant: 467638
notes: Kinetics are the same as for the craf_1* activity, ie., k1=5.5e-6, k2=0.42, k3 = 0.105 These are basedo n Force et al PNAS USA 91 1270-1274, 1994., but k1 is scaled up 5x (ie., Km is scaled down 5x to the value used here and for craf_1* activity: Km = 0.1591).
fast: false
reversible: true

467676
type: KineticLaw
local parameters: 353050
local parameters: 353047
notes: k1*MAPK_slash_MAPKK*MAPK_slash_Raf_minus_GTP_minus_Ras-k2*MAPK_slash_Raf_minus_GTP_minus_Ras_slash_Raf_minus_GTP_minus_Ras_dot_1_slash_Raf_minus_GTP_minus_Ras_dot_1_cplx

353050
type: LocalParameter
units: 462030
value: 1.8E-15

353047
type: LocalParameter
units: 462115
value: 1.41426E-14

467664
type: SpeciesReference
stoichiometry: 1.0
species: 440774

467651
type: SpeciesReference
stoichiometry: 1.0
species: 440754

467638
type: SpeciesReference
stoichiometry: 1.0
species: 440594

445373
type: Reaction
kinetic law: 467107
product: 467094
product: 467082
reactant: 467070
fast: false
reversible: false

467107
type: KineticLaw
local parameters: 353027
notes: k3*MAPK_star__slash_MAPK_star__minus_feedback_slash_MAPK_star__minus_feedback_cplx

353027
type: LocalParameter
units: 462030
value: 1.5E-14

467094
type: SpeciesReference
stoichiometry: 1.0
species: 440154

467082
type: SpeciesReference
stoichiometry: 1.0
species: 440634

467070
type: SpeciesReference
stoichiometry: 1.0
species: 440194

445653
type: Reaction
kinetic law: 467821
product: 467809
product: 467797
reactant: 467784
fast: false
reversible: false

467821
type: KineticLaw
local parameters: 353054
notes: k3*MAPK_slash_Raf_minus_GTP_minus_Ras_slash_Raf_minus_GTP_minus_Ras_dot_2_slash_Raf_minus_GTP_minus_Ras_dot_2_cplx

353054
type: LocalParameter
units: 462030
value: 4.5E-16

467809
type: SpeciesReference
stoichiometry: 1.0
species: 440754

467797
type: SpeciesReference
stoichiometry: 1.0
species: 440674

467784
type: SpeciesReference
stoichiometry: 1.0
species: 440794

443174
type: Species
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494

443833
type: Reaction
kinetic law: 463339
product: 463327
product: 463314
reactant: 463302
notes: kf = kg1 = 0.01/sec, kb = 0. This is the basal exchange of GTP for GDP.
fast: false
reversible: true

463339
type: KineticLaw
local parameters: 352824
local parameters: 352823
notes: kf*Gq_slash_G_minus_GDP-kb*G_star_GTP*BetaGamma

352824
type: LocalParameter
units: 462115
value: 0.0

352823
type: LocalParameter
units: 462030
value: 1.5E-19

463327
type: SpeciesReference
stoichiometry: 1.0
species: 440374

463314
type: SpeciesReference
stoichiometry: 1.0
species: 440394

463302
type: SpeciesReference
stoichiometry: 1.0
species: 440434

445393
type: Reaction
kinetic law: 467155
product: 467143
reactant: 467131
reactant: 467119
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

467155
type: KineticLaw
local parameters: 353029
local parameters: 353028
notes: k1*Sos_slash_Sos*MAPK_star_-k2*MAPK_star__slash_phosph_Sos_slash_phosph_Sos_cplx

353029
type: LocalParameter
units: 462030
value: 6.0E-14

353028
type: LocalParameter
units: 462115
value: 2.925045E-14

467143
type: SpeciesReference
stoichiometry: 1.0
species: 440214

467131
type: SpeciesReference
stoichiometry: 1.0
species: 440154

467119
type: SpeciesReference
stoichiometry: 1.0
species: 441654

443933
type: Reaction
kinetic law: 463773
product: 463761
reactant: 463749
reactant: 463737
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

463773
type: KineticLaw
local parameters: 352850
local parameters: 352849
notes: kf*BetaGamma*Ras_slash_inact_minus_GEF-kb*Ras_slash_GEF_minus_Gprot_minus_bg

352850
type: LocalParameter
units: 462030
value: 1.5E-15

352849
type: LocalParameter
units: 462115
value: 9.000045E-15

463761
type: SpeciesReference
stoichiometry: 1.0
species: 441034

463749
type: SpeciesReference
stoichiometry: 1.0
species: 441074

463737
type: SpeciesReference
stoichiometry: 1.0
species: 440374

443534
type: Reaction
kinetic law: 462396
product: 462383
reactant: 462371
reactant: 462359
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

462396
type: KineticLaw
local parameters: 352764
local parameters: 352761
notes: kf*PKC_slash_PKC_minus_Ca*AA-kb*PKC_slash_PKC_minus_Ca_minus_AA_star_

352764
type: LocalParameter
units: 462030
value: 1.5E-16

352761
type: LocalParameter
units: 462115
value: 1.799955E-18

462383
type: SpeciesReference
stoichiometry: 1.0
species: 439574

439574
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.75E-16
initial amount: NaN
in compartment: 439494

462371
type: SpeciesReference
stoichiometry: 1.0
species: 439774

462359
type: SpeciesReference
stoichiometry: 1.0
species: 439534

445013
type: Reaction
kinetic law: 466223
product: 466211
product: 466199
reactant: 466187
fast: false
reversible: false

466223
type: KineticLaw
local parameters: 352991
notes: k3*PKC_minus_active_slash_PKC_minus_phosph_minus_neurogranin_slash_PKC_minus_phosph_minus_neurogranin_cplx

352991
type: LocalParameter
units: 462030
value: 8.7E-16

466211
type: SpeciesReference
stoichiometry: 1.0
species: 443294

466199
type: SpeciesReference
stoichiometry: 1.0
species: 442114

466187
type: SpeciesReference
stoichiometry: 1.0
species: 439854

446973
type: Reaction
kinetic law: 471044
product: 471032
product: 471020
reactant: 471008
fast: false
reversible: false

471044
type: KineticLaw
local parameters: 353276
notes: k3*PP2A_slash_PP2A_minus_dephosph_minus_PP1_minus_I_star__slash_PP2A_minus_dephosph_minus_PP1_minus_I_star__cplx

353276
type: LocalParameter
units: 462030
value: 9.0E-15

471032
type: SpeciesReference
stoichiometry: 1.0
species: 442334

471020
type: SpeciesReference
stoichiometry: 1.0
species: 442314

471008
type: SpeciesReference
stoichiometry: 1.0
species: 442374

445153
type: Reaction
kinetic law: 466575
product: 466563
reactant: 466551
reactant: 466539
notes: 10 X raise oct 22 12 X further raise oct 24 to allow for correct conc of enzyme
fast: false
reversible: true

466575
type: KineticLaw
local parameters: 353005
local parameters: 353004
notes: k1*PLA2_slash_APC*PLA2_slash_PIP2_minus_PLA2_star_-k2*PLA2_slash_PIP2_minus_PLA2_star__slash_kenz_slash_kenz_cplx

353005
type: LocalParameter
units: 462030
value: 6.624E-14

353004
type: LocalParameter
units: 462115
value: 4.140045E-15

466563
type: SpeciesReference
stoichiometry: 1.0
species: 439994

466551
type: SpeciesReference
stoichiometry: 1.0
species: 439974

466539
type: SpeciesReference
stoichiometry: 1.0
species: 443114

443634
type: Reaction
kinetic law: 462615
product: 462603
reactant: 462591
reactant: 462579
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

462615
type: KineticLaw
local parameters: 352778
local parameters: 352777
notes: kf*PKC_slash_PKC_minus_DAG*AA-kb*PKC_slash_PKC_minus_DAG_minus_AA

352778
type: LocalParameter
units: 462030
value: 3.0E-15

352777
type: LocalParameter
units: 462115
value: 2.7E-17

462603
type: SpeciesReference
stoichiometry: 1.0
species: 439714

462591
type: SpeciesReference
stoichiometry: 1.0
species: 439774

462579
type: SpeciesReference
stoichiometry: 1.0
species: 439694

443773
type: Reaction
kinetic law: 463049
product: 463037
reactant: 463025
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

463049
type: KineticLaw
local parameters: 352806
local parameters: 352805
notes: kf*DAG-kb*PLCbeta_slash_PC

352806
type: LocalParameter
units: 462030
value: 0.0

352805
type: LocalParameter
units: 462030
value: 2.25E-16

463037
type: SpeciesReference
stoichiometry: 1.0
species: 443194

463025
type: SpeciesReference
stoichiometry: 1.0
species: 439754

445173
type: Reaction
kinetic law: 466624
product: 466612
product: 466600
reactant: 466587
fast: false
reversible: false

466624
type: KineticLaw
local parameters: 353006
notes: k3*PLA2_slash_PIP2_minus_PLA2_star__slash_kenz_slash_kenz_cplx

353006
type: LocalParameter
units: 462030
value: 1.656E-14

466612
type: SpeciesReference
stoichiometry: 1.0
species: 439974

466600
type: SpeciesReference
stoichiometry: 1.0
species: 439774

466587
type: SpeciesReference
stoichiometry: 1.0
species: 439994

445413
type: Reaction
kinetic law: 467204
product: 467192
product: 467179
reactant: 467167
fast: false
reversible: false

467204
type: KineticLaw
local parameters: 353030
notes: k3*MAPK_star__slash_phosph_Sos_slash_phosph_Sos_cplx

353030
type: LocalParameter
units: 462030
value: 1.5E-14

467192
type: SpeciesReference
stoichiometry: 1.0
species: 440154

467179
type: SpeciesReference
stoichiometry: 1.0
species: 441634

467167
type: SpeciesReference
stoichiometry: 1.0
species: 440214

444673
type: Reaction
kinetic law: 465439
product: 465427
reactant: 465415
reactant: 465403
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

465439
type: KineticLaw
local parameters: 352954
local parameters: 352953
notes: kf*PKA_minus_active*PKA_slash_PKA_minus_inhibitor-kb*PKA_slash_inhibited_minus_PKA

352954
type: LocalParameter
units: 462030
value: 1.5E-15

352953
type: LocalParameter
units: 462115
value: 9.000045E-14

465427
type: SpeciesReference
stoichiometry: 1.0
species: 442694

465415
type: SpeciesReference
stoichiometry: 1.0
species: 442674

465403
type: SpeciesReference
stoichiometry: 1.0
species: 441294

446013
type: Reaction
kinetic law: 468690
product: 468678
product: 468666
reactant: 468654
fast: false
reversible: false

468690
type: KineticLaw
local parameters: 353090
notes: k3*Ras_slash_GEF_minus_Gprot_minus_bg_slash_GEF_minus_bg_act_minus_ras_slash_GEF_minus_bg_act_minus_ras_cplx

353090
type: LocalParameter
units: 462030
value: 3.0E-17

468678
type: SpeciesReference
stoichiometry: 1.0
species: 441034

468666
type: SpeciesReference
stoichiometry: 1.0
species: 441134

468654
type: SpeciesReference
stoichiometry: 1.0
species: 441054

445813
type: Reaction
kinetic law: 468208
product: 468196
product: 468184
reactant: 468172
fast: false
reversible: false

468208
type: KineticLaw
local parameters: 353069
notes: k3*MKP_minus_1_slash_MKP1_minus_thr_minus_deph_slash_MKP1_minus_thr_minus_deph_cplx

353069
type: LocalParameter
units: 462030
value: 6.0E-15

468196
type: SpeciesReference
stoichiometry: 1.0
species: 440874

468184
type: SpeciesReference
stoichiometry: 1.0
species: 440654

468172
type: SpeciesReference
stoichiometry: 1.0
species: 440914

445053
type: Reaction
kinetic law: 466331
product: 466319
product: 466307
product: 466295
reactant: 466283
fast: false
reversible: false

466331
type: KineticLaw
local parameters: 352994
notes: k3*PKC_minus_active_slash_PKC_minus_phosph_minus_ng_minus_CaM_slash_PKC_minus_phosph_minus_ng_minus_CaM_cplx

352994
type: LocalParameter
units: 462030
value: 5.25E-16

466319
type: SpeciesReference
stoichiometry: 1.0
species: 443294

466307
type: SpeciesReference
stoichiometry: 1.0
species: 442114

466295
type: SpeciesReference
stoichiometry: 1.0
species: 442074

466283
type: SpeciesReference
stoichiometry: 1.0
species: 439874

445553
type: Reaction
kinetic law: 467578
product: 467566
reactant: 467554
reactant: 467542
notes: Rate consts same as for MAPKKtyr.
fast: false
reversible: true

467578
type: KineticLaw
local parameters: 353044
local parameters: 353043
notes: k1*MAPK_slash_MAPK_minus_tyr*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx

353044
type: LocalParameter
units: 462030
value: 1.8E-15

353043
type: LocalParameter
units: 462115
value: 4.86E-14

467566
type: SpeciesReference
stoichiometry: 1.0
species: 440714

467554
type: SpeciesReference
stoichiometry: 1.0
species: 440674

467542
type: SpeciesReference
stoichiometry: 1.0
species: 440654

443754
type: Reaction
kinetic law: 463013
product: 463001
reactant: 462989
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

463013
type: KineticLaw
local parameters: 352804
local parameters: 352803
notes: kf*IP3-kb*PLCbeta_slash_Inositol

352804
type: LocalParameter
units: 462030
value: 0.0

352803
type: LocalParameter
units: 462030
value: 3.75E-15

463001
type: SpeciesReference
stoichiometry: 1.0
species: 443174

462989
type: SpeciesReference
stoichiometry: 1.0
species: 440234

445233
type: Reaction
kinetic law: 466768
product: 466756
reactant: 466744
reactant: 466732
notes: 10 X raise oct 22 12 X raise oct 24 + conversion to k2 =4 * k3
fast: false
reversible: true

466768
type: KineticLaw
local parameters: 353014
local parameters: 353011
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

353014
type: LocalParameter
units: 462030
value: 3.6E-13

353011
type: LocalParameter
units: 462115
value: 2.250045E-14

466756
type: SpeciesReference
stoichiometry: 1.0
species: 440074

466744
type: SpeciesReference
stoichiometry: 1.0
species: 440054

466732
type: SpeciesReference
stoichiometry: 1.0
species: 443114

443993
type: Reaction
kinetic law: 463882
product: 463870
reactant: 463857
notes: Assume a reasonably good rate for dephosphorylating it, 1/sec
fast: false
reversible: true

463882
type: KineticLaw
local parameters: 352860
local parameters: 352857
notes: kf*Ras_slash_GAP_star_-kb*Ras_slash_GAP

352860
type: LocalParameter
units: 462030
value: 0.0

352857
type: LocalParameter
units: 462030
value: 1.5E-16

463870
type: SpeciesReference
stoichiometry: 1.0
species: 441194

463857
type: SpeciesReference
stoichiometry: 1.0
species: 441174

445733
type: Reaction
kinetic law: 468015
product: 468003
product: 467991
reactant: 467979
fast: false
reversible: false

468015
type: KineticLaw
local parameters: 353063
notes: k3*MAPK_slash_Raf_star__minus_GTP_minus_Ras_slash_Raf_star__minus_GTP_minus_Ras_dot_2_slash_Raf_star__minus_GTP_minus_Ras_dot_2_cplx

353063
type: LocalParameter
units: 462030
value: 4.5E-16

468003
type: SpeciesReference
stoichiometry: 1.0
species: 440814

467991
type: SpeciesReference
stoichiometry: 1.0
species: 440674

467979
type: SpeciesReference
stoichiometry: 1.0
species: 440854

446053
type: Reaction
kinetic law: 468786
product: 468774
product: 468762
reactant: 468750
fast: false
reversible: false

468786
type: KineticLaw
local parameters: 353093
notes: k3*Ras_slash_GEF_star__slash_GEF_star__minus_act_minus_ras_slash_GEF_star__minus_act_minus_ras_cplx

353093
type: LocalParameter
units: 462030
value: 3.0E-17

468774
type: SpeciesReference
stoichiometry: 1.0
species: 441094

468762
type: SpeciesReference
stoichiometry: 1.0
species: 441134

468750
type: SpeciesReference
stoichiometry: 1.0
species: 441114

444793
type: Reaction
kinetic law: 465705
product: 465693
reactant: 465681
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

465705
type: KineticLaw
local parameters: 352970
local parameters: 352969
notes: kf*AC_slash_cAMP_minus_PDE_star_-kb*AC_slash_cAMP_minus_PDE

352970
type: LocalParameter
units: 462030
value: 0.0

352969
type: LocalParameter
units: 462030
value: 1.5E-16

465693
type: SpeciesReference
stoichiometry: 1.0
species: 442894

465681
type: SpeciesReference
stoichiometry: 1.0
species: 442934

445753
type: Reaction
kinetic law: 468063
product: 468051
reactant: 468039
reactant: 468027
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

468063
type: KineticLaw
local parameters: 353065
local parameters: 353064
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

353065
type: LocalParameter
units: 462030
value: 2.4E-14

353064
type: LocalParameter
units: 462115
value: 2.250045E-13

468051
type: SpeciesReference
stoichiometry: 1.0
species: 440894

468039
type: SpeciesReference
stoichiometry: 1.0
species: 440874

468027
type: SpeciesReference
stoichiometry: 1.0
species: 440654

445473
type: Reaction
kinetic law: 467370
product: 467357
reactant: 467344
reactant: 467331
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

467370
type: KineticLaw
local parameters: 353038
local parameters: 353035
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

353038
type: LocalParameter
units: 462030
value: 2.88E-13

353035
type: LocalParameter
units: 462115
value: 7.199955E-14

467357
type: SpeciesReference
stoichiometry: 1.0
species: 440334

467344
type: SpeciesReference
stoichiometry: 1.0
species: 440314

467331
type: SpeciesReference
stoichiometry: 1.0
species: 443214

443753
type: Reaction
kinetic law: 462977
product: 462965
reactant: 462953
reactant: 462941
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

462977
type: KineticLaw
local parameters: 352802
local parameters: 352799
notes: kf*Ca*PLCbeta_slash_PLC-kb*PLCbeta_slash_PLC_minus_Ca

352802
type: LocalParameter
units: 462030
value: 1.5E-15

352799
type: LocalParameter
units: 462115
value: 4.499955E-15

462965
type: SpeciesReference
stoichiometry: 1.0
species: 440274

462953
type: SpeciesReference
stoichiometry: 1.0
species: 440254

462941
type: SpeciesReference
stoichiometry: 1.0
species: 443074

445913
type: Reaction
kinetic law: 468449
product: 468437
reactant: 468425
reactant: 468413
fast: false
reversible: true

353080
type: LocalParameter
units: 462030
value: 3.6E-14

353079
type: LocalParameter
units: 462115
value: 2.87415E-15

468437
type: SpeciesReference
stoichiometry: 1.0
species: 440994

468425
type: SpeciesReference
stoichiometry: 1.0
species: 440934

468413
type: SpeciesReference
stoichiometry: 1.0
species: 440734

445253
type: Reaction
kinetic law: 466816
product: 466804
product: 466792
reactant: 466780
fast: false
reversible: false

466816
type: KineticLaw
local parameters: 353015
notes: k3*PLA2_slash_DAG_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx

353015
type: LocalParameter
units: 462030
value: 9.0E-14

466804
type: SpeciesReference
stoichiometry: 1.0
species: 440054

466792
type: SpeciesReference
stoichiometry: 1.0
species: 439774

466780
type: SpeciesReference
stoichiometry: 1.0
species: 440074

443814
type: Reaction
kinetic law: 463290
product: 463278
reactant: 463266
reactant: 463254
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

463290
type: KineticLaw
local parameters: 352822
local parameters: 352819
notes: kf*Gq_slash_mGluR*Glu-kb*Gq_slash_Rec_minus_Glu

352822
type: LocalParameter
units: 462030
value: 1.5E-14

352819
type: LocalParameter
units: 462115
value: 2.520045E-14

463278
type: SpeciesReference
stoichiometry: 1.0
species: 440474

463266
type: SpeciesReference
stoichiometry: 1.0
species: 443154

463254
type: SpeciesReference
stoichiometry: 1.0
species: 440454

446233
type: Reaction
kinetic law: 469223
product: 469211
reactant: 469198
reactant: 469185
notes: Same rates as PKA-phosph-I1
fast: false
reversible: true

469223
type: KineticLaw
local parameters: 353113
local parameters: 353112
notes: k1*AC_slash_cAMP_minus_PDE*PKA_minus_active-k2*PKA_minus_active_slash_phosph_minus_PDE_slash_phosph_minus_PDE_cplx

353113
type: LocalParameter
units: 462030
value: 5.4E-14

353112
type: LocalParameter
units: 462115
value: 9.000045E-15

469211
type: SpeciesReference
stoichiometry: 1.0
species: 441354

469198
type: SpeciesReference
stoichiometry: 1.0
species: 441294

469185
type: SpeciesReference
stoichiometry: 1.0
species: 442894

446313
type: Reaction
kinetic law: 469416
product: 469404
reactant: 469392
reactant: 469380
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

469416
type: KineticLaw
local parameters: 353128
local parameters: 353125
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

353128
type: LocalParameter
units: 462030
value: 1.2E-15

353125
type: LocalParameter
units: 462115
value: 4.499955E-15

469404
type: SpeciesReference
stoichiometry: 1.0
species: 441474

469392
type: SpeciesReference
stoichiometry: 1.0
species: 441454

469380
type: SpeciesReference
stoichiometry: 1.0
species: 441714

445953
type: Reaction
kinetic law: 468545
product: 468533
reactant: 468521
reactant: 468509
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

353086
type: LocalParameter
units: 462030
value: 3.6E-14

353083
type: LocalParameter
units: 462115
value: 2.87415E-15

468533
type: SpeciesReference
stoichiometry: 1.0
species: 441014

468521
type: SpeciesReference
stoichiometry: 1.0
species: 440934

468509
type: SpeciesReference
stoichiometry: 1.0
species: 440634

444493
type: Reaction
kinetic law: 465006
product: 464993
reactant: 464981
reactant: 464969
notes: Disabled. See notes for PP2B7.g
fast: false
reversible: true

465006
type: KineticLaw
local parameters: 352930
local parameters: 352929
notes: kf*CaNAB_minus_Ca4*CaM_minus_TR2_minus_Ca2-kb*PP2B_slash_CaMCa2_minus_CANAB

352930
type: LocalParameter
units: 462030
value: 1.5E-15

352929
type: LocalParameter
units: 462115
value: 3.600045E-16

464993
type: SpeciesReference
stoichiometry: 1.0
species: 442494

464981
type: SpeciesReference
stoichiometry: 1.0
species: 442174

464969
type: SpeciesReference
stoichiometry: 1.0
species: 442394

445973
type: Reaction
kinetic law: 468593
product: 468581
product: 468569
reactant: 468557
fast: false
reversible: false

353087
type: LocalParameter
units: 462030
value: 9.0E-15

468581
type: SpeciesReference
stoichiometry: 1.0
species: 440934

468569
type: SpeciesReference
stoichiometry: 1.0
species: 440574

468557
type: SpeciesReference
stoichiometry: 1.0
species: 441014