MODEL9147091146
type: SBMLModel
species: 574271
notes: This is a model of ERKII signaling which is bistable due to feedback. The feedback occurs through ERKII phosphorylation of phospholipase A2 (PLA2), leading to increased production of arachidonic acid (AA), which activates protein kinase C (PKC) which activates c-Raf which is upstream of ERKII.<br""> The model is a highly simplified variant of more detailed bistable models of MAPK signaling (Bhalla US, Iyengar R. Science. 1999 Jan 15;283(5400):381-7, Ajay SM, Bhalla US. Eur J Neurosci. 2004 Nov;20(10):2671-80) This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
species: 574531
reaction: 575831
species: 574411
reaction: 576471
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species: 574491
species: 574691
reaction: 576591
reaction: 575811
reaction: 575651
reaction: 576651
units def: 479622
reaction: 576451
species: 574911
is described by: http://identifiers.org/pubmed/19404460
species: 575331
species: 575271
species: 574131
reaction: 575631
species: 574011
species: 574031
species: 574871
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volume units: 679943
reaction: 575551
species: 574771
species: 574351
species: 574511
substance units: 479721
reaction: 576851
reaction: 576551
reaction: 575771
rule: 575371
species: 574991
compartment: 573851
species: 573911
reaction: 576571
units def: 479672
species: 574651
reaction: 575451
species: 573991
species: 574211
reaction: 576771
length unit: length
reaction: 575711
reaction: 576291
reaction: 576171
reaction: 576111
reaction: 576791
species: 574711
species: 575171
species: 575291
species: 575351
species: 574051
species: 574171
reaction: 576391
species: 574311
reaction: 576331
species: 574852
species: 574471
reaction: 576511
reaction: 575691
reaction: 575431
species: 574391
reaction: 576431
units def: 479585
reaction: 576251
species: 575051
reaction: 575411
species: 574971
species: 573951
reaction: 575571
reaction: 576731
species: 574851
reaction: 576231
species: 575111
reaction: 575591

574271
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

573851
type: Compartment
constant: true
size: 1.257E-13
spatial dimensions: 3.0

574531
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

575831
type: Reaction
kinetic law: 480743
product: 480730
reactant: 480718
reactant: 480705
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

480743
type: KineticLaw
local parameters: 274488
local parameters: 274487
notes: kf*CaM_slash_CaM*Ca^2-kb*CaM_slash_CaM_minus_TR2_minus_Ca2

274488
type: LocalParameter
units: 479585
value: 9.0504E-12

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exponent: -1.0
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exponent: 1.0
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type: LocalParameter
units: 479622
value: 9.05051776470984E-12

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exponent: -1.0
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kind: SECOND

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scale: -6
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species: 575211

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constant: false
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initial concentration: 0.0
initial amount: NaN
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480718
type: SpeciesReference
stoichiometry: 2.0
species: 574852

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type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.08
initial amount: NaN
in compartment: 573851

480705
type: SpeciesReference
stoichiometry: 1.0
species: 575171

575171
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 20.0
initial amount: NaN
in compartment: 573851

574411
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.59997348183506
initial amount: NaN
in compartment: 573851

576471
type: Reaction
kinetic law: 482283
product: 482271
product: 482259
reactant: 482247
fast: false
reversible: false

482283
type: KineticLaw
local parameters: 274563
notes: k3*Ras_slash_GAP_slash_GAP_minus_inact_minus_ras_slash_GAP_minus_inact_minus_ras_cplx

274563
type: LocalParameter
units: 479585
value: 1.257E-12

482271
type: SpeciesReference
stoichiometry: 1.0
species: 574791

574791
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constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.01
initial amount: NaN
in compartment: 573851

482259
type: SpeciesReference
stoichiometry: 1.0
species: 574751

574751
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 573851

482247
type: SpeciesReference
stoichiometry: 1.0
species: 574811

574811
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

574371
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

574491
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

574691
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

576591
type: Reaction
kinetic law: 482572
product: 482560
product: 482548
reactant: 482536
fast: false
reversible: false

482572
type: KineticLaw
local parameters: 274578
notes: k3*PKC_minus_active_slash_PKC_minus_inact_minus_GAP_slash_PKC_minus_inact_minus_GAP_cplx

274578
type: LocalParameter
units: 479585
value: 5.028E-13

482560
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stoichiometry: 1.0
species: 575351

575351
type: Species
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.3
initial amount: NaN
in compartment: 573851

482548
type: SpeciesReference
stoichiometry: 1.0
species: 574771

574771
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

482536
type: SpeciesReference
stoichiometry: 1.0
species: 574891

574891
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

575811
type: Reaction
kinetic law: 480693
product: 480681
reactant: 480669
reactant: 480657
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 28 Feb 2006: Increased affinity 36-fold to account for Ca input to MAPK cascade, possibly folding in other pathway inputs. 21 April 2006: Altered affinity to same level as pkm_mapk21.g model to prevent spontaneous turnon. Kf = 200, Kb = 1.
fast: false
reversible: true

480693
type: KineticLaw
local parameters: 274486
local parameters: 274485
notes: kf*Ras_slash_inact_minus_GEF*CaM_slash_CaM_minus_Ca4-kb*Ras_slash_CaM_minus_GEF

274486
type: LocalParameter
units: 479585
value: 1.257E-13

274485
type: LocalParameter
units: 479672
value: 2.51398436292E-11

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kind: SECOND

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exponent: -1.0
scale: -6
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kind: MOLE

479685
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kind: LITRE

480681
type: SpeciesReference
stoichiometry: 1.0
species: 574831

574831
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

480669
type: SpeciesReference
stoichiometry: 1.0
species: 575231

575231
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

480657
type: SpeciesReference
stoichiometry: 1.0
species: 574651

574651
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.1
initial amount: NaN
in compartment: 573851

575651
type: Reaction
kinetic law: 480367
product: 480355
reactant: 480342
reactant: 480330
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

480367
type: KineticLaw
local parameters: 274470
local parameters: 274469
notes: kf*DAG*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_DAG_minus_Ca_minus_PLA2_star_

274470
type: LocalParameter
units: 479585
value: 5.028E-13

274469
type: LocalParameter
units: 479672
value: 3.77097654438E-16

480355
type: SpeciesReference
stoichiometry: 1.0
species: 574251

574251
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

480342
type: SpeciesReference
stoichiometry: 1.0
species: 574131

574131
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

480330
type: SpeciesReference
stoichiometry: 1.0
species: 575291

575291
type: Species
constant: true
boundary condition: true
has only substance units: false
initial concentration: 12.1999469636701
initial amount: NaN
in compartment: 573851

576651
type: Reaction
kinetic law: 482718
product: 482706
reactant: 482694
reactant: 482682
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

482718
type: KineticLaw
local parameters: 274587
local parameters: 274585
notes: k1*PLA2_slash_PLA2_minus_cytosolic*MAPK_star_-k2*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx

274587
type: LocalParameter
units: 479585
value: 5.028E-12

274585
type: LocalParameter
units: 479672
value: 2.45122481664E-13

482706
type: SpeciesReference
stoichiometry: 1.0
species: 574971

574971
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

482694
type: SpeciesReference
stoichiometry: 1.0
species: 574951

574951
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

482682
type: SpeciesReference
stoichiometry: 1.0
species: 574111

574111
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.4
initial amount: NaN
in compartment: 573851

576451
type: Reaction
kinetic law: 482235
product: 482223
reactant: 482211
reactant: 482199
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

482235
type: KineticLaw
local parameters: 274562
local parameters: 274560
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

274562
type: LocalParameter
units: 479585
value: 5.028E-12

274560
type: LocalParameter
units: 479672
value: 6.22030530222E-12

482223
type: SpeciesReference
stoichiometry: 1.0
species: 574811

482211
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stoichiometry: 1.0
species: 574791

482199
type: SpeciesReference
stoichiometry: 1.0
species: 574731

574731
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

574911
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

575331
type: Species
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.08
initial amount: NaN
in compartment: 573851

575271
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: 573851

575631
type: Reaction
kinetic law: 480317
product: 480305
reactant: 480293
reactant: 480281
fast: false
reversible: true

480317
type: KineticLaw
local parameters: 274468
local parameters: 274466
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star_

274468
type: LocalParameter
units: 479585
value: 1.257E-14

274466
type: LocalParameter
units: 479672
value: 1.50840957834E-15

480305
type: SpeciesReference
stoichiometry: 1.0
species: 574211

574211
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

480293
type: SpeciesReference
stoichiometry: 1.0
species: 574131

480281
type: SpeciesReference
stoichiometry: 1.0
species: 575271

574011
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 8.46313975072925E-23
initial amount: NaN
in compartment: 573851

574031
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.16100503845134E-16
initial amount: NaN
in compartment: 573851

574871
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

576051
type: Reaction
kinetic law: 481265
product: 481253
reactant: 481241
reactant: 481229
notes: 10 X raise oct 22 12 X raise oct 24 + conversion to k2 =4 * k3
fast: false
reversible: true

481265
type: KineticLaw
local parameters: 274512
local parameters: 274510
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

274512
type: LocalParameter
units: 479585
value: 3.0168E-11

274510
type: LocalParameter
units: 479672
value: 1.88553567366E-12

481253
type: SpeciesReference
stoichiometry: 1.0
species: 574271

481241
type: SpeciesReference
stoichiometry: 1.0
species: 574251

481229
type: SpeciesReference
stoichiometry: 1.0
species: 575251

575251
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: 573851

575551
type: Reaction
kinetic law: 480123
product: 480111
reactant: 480099
reactant: 480086
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

480123
type: KineticLaw
local parameters: 274459
local parameters: 274458
notes: kf*PKC_slash_PKC_minus_cytosolic*DAG-kb*PKC_slash_PKC_minus_DAG

274459
type: LocalParameter
units: 479585
value: 1.257E-14

274458
type: LocalParameter
units: 479672
value: 7.5420478917E-17

480111
type: SpeciesReference
stoichiometry: 1.0
species: 574031

480099
type: SpeciesReference
stoichiometry: 1.0
species: 575291

480086
type: SpeciesReference
stoichiometry: 1.0
species: 574071

574071
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 573851

574351
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 573851

574511
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

479733
type: SBMLUnit
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE

576851
type: Reaction
kinetic law: 483200
product: 483188
reactant: 483176
reactant: 483164
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

274612
type: LocalParameter
units: 479585
value: 3.0168E-12

274610
type: LocalParameter
units: 479672
value: 2.40856349364E-13

483188
type: SpeciesReference
stoichiometry: 1.0
species: 575111

575111
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

483176
type: SpeciesReference
stoichiometry: 1.0
species: 575071

575071
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 573851

483164
type: SpeciesReference
stoichiometry: 1.0
species: 574471

574471
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

576551
type: Reaction
kinetic law: 482475
product: 482463
product: 482451
reactant: 482439
fast: false
reversible: false

482475
type: KineticLaw
local parameters: 274573
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_raf_slash_PKC_minus_act_minus_raf_cplx

274573
type: LocalParameter
units: 479585
value: 5.028E-13

482463
type: SpeciesReference
stoichiometry: 1.0
species: 575351

482451
type: SpeciesReference
stoichiometry: 1.0
species: 574371

482439
type: SpeciesReference
stoichiometry: 1.0
species: 574871

575771
type: Reaction
kinetic law: 480608
product: 480596
reactant: 480584
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

480608
type: KineticLaw
local parameters: 274482
local parameters: 274481
notes: kf*Ras_slash_GTP_minus_Ras-kb*Ras_slash_GDP_minus_Ras

274482
type: LocalParameter
units: 479585
value: 0.0

274481
type: LocalParameter
units: 479585
value: 1.257E-17

480596
type: SpeciesReference
stoichiometry: 1.0
species: 574751

480584
type: SpeciesReference
stoichiometry: 1.0
species: 574731

574991
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

573911
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.75006629541236E-16
initial amount: NaN
in compartment: 573851

576571
type: Reaction
kinetic law: 482524
product: 482512
reactant: 482500
reactant: 482487
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

482524
type: KineticLaw
local parameters: 274577
local parameters: 274575
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

274577
type: LocalParameter
units: 479585
value: 2.0112E-12

274575
type: LocalParameter
units: 479672
value: 7.5420478917E-13

482512
type: SpeciesReference
stoichiometry: 1.0
species: 574891

482500
type: SpeciesReference
stoichiometry: 1.0
species: 575351

482487
type: SpeciesReference
stoichiometry: 1.0
species: 574791

575451
type: Reaction
kinetic law: 479903
product: 479890
reactant: 479878
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

479903
type: KineticLaw
local parameters: 274449
local parameters: 274448
notes: kf*PKC_slash_PKC_minus_Ca_minus_DAG-kb*PKC_slash_PKC_minus_DAG_minus_memb_star_

274449
type: LocalParameter
units: 479585
value: 1.257E-14

274448
type: LocalParameter
units: 479585
value: 1.257E-13

479890
type: SpeciesReference
stoichiometry: 1.0
species: 573951

573951
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 9.4351630867144E-21
initial amount: NaN
in compartment: 573851

479878
type: SpeciesReference
stoichiometry: 1.0
species: 574011

573991
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.81331211880138E-17
initial amount: NaN
in compartment: 573851

576771
type: Reaction
kinetic law: 483006
product: 482994
reactant: 482982
reactant: 482970
notes: See MKP1-tyr-deph
fast: false
reversible: true

483006
type: KineticLaw
local parameters: 274602
local parameters: 274600
notes: k1*MAPK_star_*MKP_minus_1-k2*MKP_minus_1_slash_MKP1_minus_thr_minus_deph_slash_MKP1_minus_thr_minus_deph_cplx

274602
type: LocalParameter
units: 479585
value: 2.0112E-12

274600
type: LocalParameter
units: 479672
value: 1.88553567366E-11

482994
type: SpeciesReference
stoichiometry: 1.0
species: 575051

575051
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

482982
type: SpeciesReference
stoichiometry: 1.0
species: 575011

575011
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0240002651816494
initial amount: NaN
in compartment: 573851

482970
type: SpeciesReference
stoichiometry: 1.0
species: 574951

575711
type: Reaction
kinetic law: 480487
product: 480475
reactant: 480463
fast: false
reversible: true

480487
type: KineticLaw
local parameters: 274476
local parameters: 274475
notes: kf*PLA2_slash_PLA2_star_-kb*PLA2_slash_PLA2_minus_cytosolic

274476
type: LocalParameter
units: 479585
value: 0.0

274475
type: LocalParameter
units: 479585
value: 2.1369E-14

480475
type: SpeciesReference
stoichiometry: 1.0
species: 574111

480463
type: SpeciesReference
stoichiometry: 1.0
species: 574331

574331
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

576291
type: Reaction
kinetic law: 481848
product: 481835
reactant: 481823
reactant: 481811
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

481848
type: KineticLaw
local parameters: 274542
local parameters: 274540
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

274542
type: LocalParameter
units: 479585
value: 1.5084E-13

274540
type: LocalParameter
units: 479672
value: 1.18513155294E-12

481835
type: SpeciesReference
stoichiometry: 1.0
species: 574611

574611
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

481823
type: SpeciesReference
stoichiometry: 1.0
species: 574591

574591
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

481811
type: SpeciesReference
stoichiometry: 1.0
species: 574391

574391
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 573851

576171
type: Reaction
kinetic law: 481556
product: 481543
reactant: 481531
reactant: 481519
notes: Rate consts same as for MAPKKtyr.
fast: false
reversible: true

481556
type: KineticLaw
local parameters: 274527
local parameters: 274525
notes: k1*MAPK_slash_MAPK_minus_tyr*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx

274527
type: LocalParameter
units: 479585
value: 1.5084E-13

274525
type: LocalParameter
units: 479672
value: 4.07263949946E-12

481543
type: SpeciesReference
stoichiometry: 1.0
species: 574511

481531
type: SpeciesReference
stoichiometry: 1.0
species: 574471

481519
type: SpeciesReference
stoichiometry: 1.0
species: 574451

574451
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

576111
type: Reaction
kinetic law: 481409
product: 481397
product: 481385
reactant: 481373
fast: false
reversible: false

481409
type: KineticLaw
local parameters: 274518
notes: k3*PLA2_slash_PLA2_star__minus_Ca_slash_kenz_slash_kenz_cplx

274518
type: LocalParameter
units: 479585
value: 1.5084E-11

481397
type: SpeciesReference
stoichiometry: 1.0
species: 574291

574291
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

481385
type: SpeciesReference
stoichiometry: 1.0
species: 574091

574091
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

481373
type: SpeciesReference
stoichiometry: 1.0
species: 574311

574311
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

576791
type: Reaction
kinetic law: 483055
product: 483042
product: 483030
reactant: 483018
fast: false
reversible: false

483055
type: KineticLaw
local parameters: 274603
notes: k3*MKP_minus_1_slash_MKP1_minus_thr_minus_deph_slash_MKP1_minus_thr_minus_deph_cplx

274603
type: LocalParameter
units: 479585
value: 5.028E-13

483042
type: SpeciesReference
stoichiometry: 1.0
species: 575011

483030
type: SpeciesReference
stoichiometry: 1.0
species: 574451

483018
type: SpeciesReference
stoichiometry: 1.0
species: 575051

574711
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

574051
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 2.51882789710952E-19
initial amount: NaN
in compartment: 573851

574171
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

576391
type: Reaction
kinetic law: 482091
product: 482079
product: 482067
reactant: 482055
fast: false
reversible: false

482091
type: KineticLaw
local parameters: 274553
notes: k3*Ras_slash_inact_minus_GEF_slash_basal_GEF_activity_slash_basal_GEF_activity_cplx

274553
type: LocalParameter
units: 479585
value: 2.514E-15

482079
type: SpeciesReference
stoichiometry: 1.0
species: 574651

482067
type: SpeciesReference
stoichiometry: 1.0
species: 574731

482055
type: SpeciesReference
stoichiometry: 1.0
species: 574671

574671
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

576331
type: Reaction
kinetic law: 481944
product: 481932
reactant: 481920
reactant: 481908
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

481944
type: KineticLaw
local parameters: 274547
local parameters: 274545
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

274547
type: LocalParameter
units: 479585
value: 1.5084E-13

274545
type: LocalParameter
units: 479672
value: 1.18513155294E-12

481932
type: SpeciesReference
stoichiometry: 1.0
species: 574631

574631
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

481920
type: SpeciesReference
stoichiometry: 1.0
species: 574591

481908
type: SpeciesReference
stoichiometry: 1.0
species: 574531

576511
type: Reaction
kinetic law: 482379
product: 482367
product: 482355
reactant: 482343
fast: false
reversible: false

482379
type: KineticLaw
local parameters: 274568
notes: k3*Ras_slash_CaM_minus_GEF_slash_CaM_minus_GEF_minus_act_minus_ras_slash_CaM_minus_GEF_minus_act_minus_ras_cplx

274568
type: LocalParameter
units: 479585
value: 1.257E-14

482367
type: SpeciesReference
stoichiometry: 1.0
species: 574831

482355
type: SpeciesReference
stoichiometry: 1.0
species: 574731

482343
type: SpeciesReference
stoichiometry: 1.0
species: 574851

574851
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

575691
type: Reaction
kinetic law: 480451
product: 480439
reactant: 480427
reactant: 480415
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

480451
type: KineticLaw
local parameters: 274474
local parameters: 274473
notes: kf*PLA2_slash_PLA2_star_*Ca-kb*PLA2_slash_PLA2_star__minus_Ca

274474
type: LocalParameter
units: 479585
value: 1.257E-14

274473
type: LocalParameter
units: 479672
value: 7.5420478917E-13

480439
type: SpeciesReference
stoichiometry: 1.0
species: 574291

480427
type: SpeciesReference
stoichiometry: 1.0
species: 574852

480415
type: SpeciesReference
stoichiometry: 1.0
species: 574331

575431
type: Reaction
kinetic law: 479866
product: 479854
reactant: 479842
fast: false
reversible: true

479866
type: KineticLaw
local parameters: 274447
local parameters: 274446
notes: kf*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_memb_star_

274447
type: LocalParameter
units: 479585
value: 4.4027682E-13

274446
type: LocalParameter
units: 479585
value: 1.5970185E-13

479854
type: SpeciesReference
stoichiometry: 1.0
species: 573931

573931
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.38955184301246E-17
initial amount: NaN
in compartment: 573851

479842
type: SpeciesReference
stoichiometry: 1.0
species: 573871

573871
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.72076372315036E-17
initial amount: NaN
in compartment: 573851

576431
type: Reaction
kinetic law: 482187
product: 482175
product: 482163
reactant: 482151
fast: false
reversible: false

482187
type: KineticLaw
local parameters: 274558
notes: k3*Ras_slash_GEF_star__slash_GEF_star__minus_act_minus_ras_slash_GEF_star__minus_act_minus_ras_cplx

274558
type: LocalParameter
units: 479585
value: 2.514E-15

482175
type: SpeciesReference
stoichiometry: 1.0
species: 574691

482163
type: SpeciesReference
stoichiometry: 1.0
species: 574731

482151
type: SpeciesReference
stoichiometry: 1.0
species: 574711

576251
type: Reaction
kinetic law: 481750
product: 481738
reactant: 481726
reactant: 481714
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

481750
type: KineticLaw
local parameters: 274537
local parameters: 274535
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

274537
type: LocalParameter
units: 479585
value: 1.5084E-13

274535
type: LocalParameter
units: 479672
value: 1.18513155294E-12

481738
type: SpeciesReference
stoichiometry: 1.0
species: 574571

574571
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

481726
type: SpeciesReference
stoichiometry: 1.0
species: 574551

574551
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

481714
type: SpeciesReference
stoichiometry: 1.0
species: 574531

575411
type: Reaction
kinetic law: 479830
product: 479818
reactant: 479806
reactant: 479794
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

479830
type: KineticLaw
local parameters: 274445
local parameters: 274443
notes: kf*DAG*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_DAG

274445
type: LocalParameter
units: 479585
value: 1.08539436E-12

274443
type: LocalParameter
units: 479672
value: 1.00557478458E-15

479818
type: SpeciesReference
stoichiometry: 1.0
species: 574011

479806
type: SpeciesReference
stoichiometry: 1.0
species: 573871

479794
type: SpeciesReference
stoichiometry: 1.0
species: 575291

575571
type: Reaction
kinetic law: 480172
product: 480160
reactant: 480147
reactant: 480135
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

480172
type: KineticLaw
local parameters: 274461
local parameters: 274460
notes: kf*PKC_slash_PKC_minus_DAG*AA-kb*PKC_slash_PKC_minus_DAG_minus_AA

274461
type: LocalParameter
units: 479585
value: 2.514E-13

274460
type: LocalParameter
units: 479672
value: 2.26256696604E-15

480160
type: SpeciesReference
stoichiometry: 1.0
species: 574051

480147
type: SpeciesReference
stoichiometry: 1.0
species: 574091

480135
type: SpeciesReference
stoichiometry: 1.0
species: 574031

576731
type: Reaction
kinetic law: 482910
product: 482898
reactant: 482886
reactant: 482874
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

482910
type: KineticLaw
local parameters: 274597
local parameters: 274595
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

274597
type: LocalParameter
units: 479585
value: 2.0112E-12

274595
type: LocalParameter
units: 479672
value: 1.88553567366E-11

482898
type: SpeciesReference
stoichiometry: 1.0
species: 575031

575031
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

482886
type: SpeciesReference
stoichiometry: 1.0
species: 575011

482874
type: SpeciesReference
stoichiometry: 1.0
species: 574451

576231
type: Reaction
kinetic law: 481701
product: 481689
product: 481677
reactant: 481665
fast: false
reversible: false

481701
type: KineticLaw
local parameters: 274533
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

274533
type: LocalParameter
units: 479585
value: 3.771E-14

481689
type: SpeciesReference
stoichiometry: 1.0
species: 574551

481677
type: SpeciesReference
stoichiometry: 1.0
species: 574531

481665
type: SpeciesReference
stoichiometry: 1.0
species: 574552

574552
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

575591
type: Reaction
kinetic law: 480221
product: 480209
reactant: 480197
reactant: 480184
notes: Leslie and Channon BBA 1045 (1990) 261-270 fig6 pp267.
fast: false
reversible: true

480221
type: KineticLaw
local parameters: 274463
local parameters: 274462
notes: kf*PLA2_slash_PLA2_minus_cytosolic*Ca-kb*PLA2_slash_PLA2_minus_Ca_star_

274463
type: LocalParameter
units: 479585
value: 1.257E-14

274462
type: LocalParameter
units: 479672
value: 1.25699218146E-13

480209
type: SpeciesReference
stoichiometry: 1.0
species: 574131

480197
type: SpeciesReference
stoichiometry: 1.0
species: 574852

480184
type: SpeciesReference
stoichiometry: 1.0
species: 574111

575791
type: Reaction
kinetic law: 480645
product: 480633
reactant: 480620
notes: Assume a reasonably good rate for dephosphorylating it, 1/sec
fast: false
reversible: true

480645
type: KineticLaw
local parameters: 274484
local parameters: 274483
notes: kf*Ras_slash_GAP_star_-kb*Ras_slash_GAP

274484
type: LocalParameter
units: 479585
value: 0.0

274483
type: LocalParameter
units: 479585
value: 1.257E-14

480633
type: SpeciesReference
stoichiometry: 1.0
species: 574791

480620
type: SpeciesReference
stoichiometry: 1.0
species: 574771

576811
type: Reaction
kinetic law: 483104
product: 483092
reactant: 483080
reactant: 483068
notes: See parent PPhosphatase2A for parms
fast: false
reversible: true

274607
type: LocalParameter
units: 479585
value: 3.0168E-12

274605
type: LocalParameter
units: 479672
value: 2.40856349364E-13

483092
type: SpeciesReference
stoichiometry: 1.0
species: 575091

575091
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

483080
type: SpeciesReference
stoichiometry: 1.0
species: 575071

483068
type: SpeciesReference
stoichiometry: 1.0
species: 574371

575191
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

575951
type: Reaction
kinetic law: 481022
product: 481010
product: 480998
reactant: 480986
fast: false
reversible: false

481022
type: KineticLaw
local parameters: 274500
notes: k3*PLA2_slash_PLA2_minus_Ca_star__slash_kenz_slash_kenz_cplx

274500
type: LocalParameter
units: 479585
value: 6.7878E-13

481010
type: SpeciesReference
stoichiometry: 1.0
species: 574131

480998
type: SpeciesReference
stoichiometry: 1.0
species: 574091

480986
type: SpeciesReference
stoichiometry: 1.0
species: 574151

574151
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

576831
type: Reaction
kinetic law: 483152
product: 483140
product: 483128
reactant: 483116
fast: false
reversible: false

274608
type: LocalParameter
units: 479585
value: 7.542E-13

483140
type: SpeciesReference
stoichiometry: 1.0
species: 575071

483128
type: SpeciesReference
stoichiometry: 1.0
species: 574351

483116
type: SpeciesReference
stoichiometry: 1.0
species: 575091

575491
type: Reaction
kinetic law: 479988
product: 479975
reactant: 479963
notes: Assume slowish too. Schaechter and Benowitz
fast: false
reversible: true

479988
type: KineticLaw
local parameters: 274453
local parameters: 274452
notes: kf*PKC_slash_PKC_minus_DAG_minus_AA-kb*PKC_slash_PKC_minus_DAG_minus_AA_star_

274453
type: LocalParameter
units: 479585
value: 2.514E-14

274452
type: LocalParameter
units: 479585
value: 2.514E-13

479975
type: SpeciesReference
stoichiometry: 1.0
species: 573891

573891
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 4.91368337311058E-18
initial amount: NaN
in compartment: 573851

479963
type: SpeciesReference
stoichiometry: 1.0
species: 574051

576631
type: Reaction
kinetic law: 482670
product: 482658
product: 482646
reactant: 482633
fast: false
reversible: false

482670
type: KineticLaw
local parameters: 274583
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_GEF_slash_PKC_minus_act_minus_GEF_cplx

274583
type: LocalParameter
units: 479585
value: 5.028E-13

482658
type: SpeciesReference
stoichiometry: 1.0
species: 575351

482646
type: SpeciesReference
stoichiometry: 1.0
species: 574691

482633
type: SpeciesReference
stoichiometry: 1.0
species: 574911

576491
type: Reaction
kinetic law: 482331
product: 482319
reactant: 482307
reactant: 482295
notes: Kinetics same as GEF-bg_act-ras
fast: false
reversible: true

482331
type: KineticLaw
local parameters: 274567
local parameters: 274565
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

274567
type: LocalParameter
units: 479585
value: 5.028E-14

274565
type: LocalParameter
units: 479672
value: 1.24447819338E-13

482319
type: SpeciesReference
stoichiometry: 1.0
species: 574851

482307
type: SpeciesReference
stoichiometry: 1.0
species: 574831

482295
type: SpeciesReference
stoichiometry: 1.0
species: 574751

574431
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

575991
type: Reaction
kinetic law: 481120
product: 481108
product: 481096
reactant: 481083
fast: false
reversible: false

481120
type: KineticLaw
local parameters: 274503
notes: k3*PLA2_slash_PIP2_minus_PLA2_star__slash_kenz_slash_kenz_cplx

274503
type: LocalParameter
units: 479585
value: 1.387728E-12

481108
type: SpeciesReference
stoichiometry: 1.0
species: 574171

481096
type: SpeciesReference
stoichiometry: 1.0
species: 574091

481083
type: SpeciesReference
stoichiometry: 1.0
species: 574191

574191
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

576211
type: Reaction
kinetic law: 481653
product: 481640
reactant: 481628
reactant: 481616
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

481653
type: KineticLaw
local parameters: 274532
local parameters: 274530
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

274532
type: LocalParameter
units: 479585
value: 1.5084E-13

274530
type: LocalParameter
units: 479672
value: 1.18513155294E-12

481640
type: SpeciesReference
stoichiometry: 1.0
species: 574552

481628
type: SpeciesReference
stoichiometry: 1.0
species: 574551

481616
type: SpeciesReference
stoichiometry: 1.0
species: 574391

576071
type: Reaction
kinetic law: 481313
product: 481301
product: 481289
reactant: 481277
fast: false
reversible: false

481313
type: KineticLaw
local parameters: 274513
notes: k3*PLA2_slash_DAG_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx

274513
type: LocalParameter
units: 479585
value: 7.542E-12

481301
type: SpeciesReference
stoichiometry: 1.0
species: 574251

481289
type: SpeciesReference
stoichiometry: 1.0
species: 574091

481277
type: SpeciesReference
stoichiometry: 1.0
species: 574271

574931
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

575531
type: Reaction
kinetic law: 480074
product: 480062
reactant: 480050
reactant: 480038
notes: Raise kf from 1.667e-10 to 2e-10 to get better match to data.
fast: false
reversible: true

480074
type: KineticLaw
local parameters: 274457
local parameters: 274456
notes: kf*AA*PKC_slash_PKC_minus_cytosolic-kb*PKC_slash_PKC_minus_AA_star_

274457
type: LocalParameter
units: 479585
value: 1.257E-14

274456
type: LocalParameter
units: 479672
value: 1.50840957834E-17

480062
type: SpeciesReference
stoichiometry: 1.0
species: 573991

480050
type: SpeciesReference
stoichiometry: 1.0
species: 574071

480038
type: SpeciesReference
stoichiometry: 1.0
species: 574091

576931
type: Reaction
kinetic law: 483394
product: 483382
reactant: 483369
reactant: 483357
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

274625
type: LocalParameter
units: 479585
value: 3.0168E-12

274620
type: LocalParameter
units: 479672
value: 2.40856349364E-13

483382
type: SpeciesReference
stoichiometry: 1.0
species: 575151

575151
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

483369
type: SpeciesReference
stoichiometry: 1.0
species: 575071

483357
type: SpeciesReference
stoichiometry: 1.0
species: 574431

575891
type: Reaction
kinetic law: 480890
product: 480878
reactant: 480865
reactant: 480853
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

480890
type: KineticLaw
local parameters: 274495
local parameters: 274494
notes: kf*MAPK_slash_craf_minus_1*Ras_slash_GTP_minus_Ras-kb*MAPK_slash_Raf_minus_GTP_minus_Ras

274495
type: LocalParameter
units: 479585
value: 1.257E-13

274494
type: LocalParameter
units: 479672
value: 7.5420478917E-13

480878
type: SpeciesReference
stoichiometry: 1.0
species: 574551

480865
type: SpeciesReference
stoichiometry: 1.0
species: 574731

480853
type: SpeciesReference
stoichiometry: 1.0
species: 574351

576311
type: Reaction
kinetic law: 481896
product: 481884
product: 481872
reactant: 481860
fast: false
reversible: false

481896
type: KineticLaw
local parameters: 274543
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

274543
type: LocalParameter
units: 479585
value: 3.771E-14

481884
type: SpeciesReference
stoichiometry: 1.0
species: 574591

481872
type: SpeciesReference
stoichiometry: 1.0
species: 574531

481860
type: SpeciesReference
stoichiometry: 1.0
species: 574611

575971
type: Reaction
kinetic law: 481071
product: 481059
reactant: 481046
reactant: 481034
notes: 10 X raise oct 22 12 X further raise oct 24 to allow for correct conc of enzyme
fast: false
reversible: true

481071
type: KineticLaw
local parameters: 274502
local parameters: 274501
notes: k1*PLA2_slash_APC*PLA2_slash_PIP2_minus_PLA2_star_-k2*PLA2_slash_PIP2_minus_PLA2_star__slash_kenz_slash_kenz_cplx

274502
type: LocalParameter
units: 479585
value: 5.550912E-12

274501
type: LocalParameter
units: 479672
value: 3.4693135893E-13

481059
type: SpeciesReference
stoichiometry: 1.0
species: 574191

481046
type: SpeciesReference
stoichiometry: 1.0
species: 574171

481034
type: SpeciesReference
stoichiometry: 1.0
species: 575251

575131
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

575751
type: Reaction
kinetic law: 480572
product: 480559
reactant: 480547
fast: false
reversible: true

480572
type: KineticLaw
local parameters: 274480
local parameters: 274479
notes: kf*Ras_slash_GEF_star_-kb*Ras_slash_inact_minus_GEF

274480
type: LocalParameter
units: 479585
value: 0.0

274479
type: LocalParameter
units: 479585
value: 1.257E-13

480559
type: SpeciesReference
stoichiometry: 1.0
species: 574651

480547
type: SpeciesReference
stoichiometry: 1.0
species: 574691

575471
type: Reaction
kinetic law: 479951
product: 479939
reactant: 479927
reactant: 479915
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

479951
type: KineticLaw
local parameters: 274451
local parameters: 274450
notes: kf*PKC_slash_PKC_minus_Ca*AA-kb*PKC_slash_PKC_minus_Ca_minus_AA_star_

274451
type: LocalParameter
units: 479585
value: 1.257E-14

274450
type: LocalParameter
units: 479672
value: 1.50840957834E-16

479939
type: SpeciesReference
stoichiometry: 1.0
species: 573911

479927
type: SpeciesReference
stoichiometry: 1.0
species: 574091

479915
type: SpeciesReference
stoichiometry: 1.0
species: 573871

575911
type: Reaction
kinetic law: 480926
product: 480914
reactant: 480902
fast: false
reversible: true

480926
type: KineticLaw
local parameters: 274497
local parameters: 274496
notes: kf*Ca_input-kb*Ca

274497
type: LocalParameter
units: 479585
value: 2.514E-13

274496
type: LocalParameter
units: 479585
value: 2.514E-13

480914
type: SpeciesReference
stoichiometry: 1.0
species: 574852

480902
type: SpeciesReference
stoichiometry: 1.0
species: 575331

576031
type: Reaction
kinetic law: 481216
product: 481204
product: 481192
reactant: 481180
fast: false
reversible: false

481216
type: KineticLaw
local parameters: 274508
notes: k3*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx

274508
type: LocalParameter
units: 479585
value: 4.5252E-12

481204
type: SpeciesReference
stoichiometry: 1.0
species: 574211

481192
type: SpeciesReference
stoichiometry: 1.0
species: 574091

481180
type: SpeciesReference
stoichiometry: 1.0
species: 574231

574231
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

576151
type: Reaction
kinetic law: 481506
product: 481493
product: 481481
reactant: 481469
fast: false
reversible: false

481506
type: KineticLaw
local parameters: 274523
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx

274523
type: LocalParameter
units: 479585
value: 3.771E-14

481493
type: SpeciesReference
stoichiometry: 1.0
species: 574471

481481
type: SpeciesReference
stoichiometry: 1.0
species: 574451

481469
type: SpeciesReference
stoichiometry: 1.0
species: 574491

576911
type: Reaction
kinetic law: 483345
product: 483333
product: 483321
reactant: 483309
fast: false
reversible: false

274618
type: LocalParameter
units: 479585
value: 7.542E-13

483333
type: SpeciesReference
stoichiometry: 1.0
species: 575071

483321
type: SpeciesReference
stoichiometry: 1.0
species: 574391

483309
type: SpeciesReference
stoichiometry: 1.0
species: 575131

576011
type: Reaction
kinetic law: 481168
product: 481156
reactant: 481144
reactant: 481132
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

481168
type: KineticLaw
local parameters: 274507
local parameters: 274505
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

274507
type: LocalParameter
units: 479585
value: 1.81008E-11

274505
type: LocalParameter
units: 479672
value: 1.13128348302E-12

481156
type: SpeciesReference
stoichiometry: 1.0
species: 574231

481144
type: SpeciesReference
stoichiometry: 1.0
species: 574211

481132
type: SpeciesReference
stoichiometry: 1.0
species: 575251

576951
type: Reaction
kinetic law: 483442
product: 483430
product: 483418
reactant: 483406
fast: false
reversible: false

274627
type: LocalParameter
units: 479585
value: 7.542E-13

483430
type: SpeciesReference
stoichiometry: 1.0
species: 575071

483418
type: SpeciesReference
stoichiometry: 1.0
species: 574371

483406
type: SpeciesReference
stoichiometry: 1.0
species: 575151

576711
type: Reaction
kinetic law: 482862
product: 482850
product: 482838
reactant: 482826
fast: false
reversible: false

482862
type: KineticLaw
local parameters: 274593
notes: k3*MAPK_star__slash_MAPK_star__minus_feedback_slash_MAPK_star__minus_feedback_cplx

274593
type: LocalParameter
units: 479585
value: 1.257E-12

482850
type: SpeciesReference
stoichiometry: 1.0
species: 574951

482838
type: SpeciesReference
stoichiometry: 1.0
species: 574431

482826
type: SpeciesReference
stoichiometry: 1.0
species: 574991

575871
type: Reaction
kinetic law: 480840
product: 480827
reactant: 480815
reactant: 480803
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

480840
type: KineticLaw
local parameters: 274493
local parameters: 274492
notes: kf*CaM_slash_CaM_minus_Ca3*Ca-kb*CaM_slash_CaM_minus_Ca4

274493
type: LocalParameter
units: 479585
value: 1.257E-12

274492
type: LocalParameter
units: 479672
value: 5.8450752657E-14

480827
type: SpeciesReference
stoichiometry: 1.0
species: 575231

480815
type: SpeciesReference
stoichiometry: 1.0
species: 574852

480803
type: SpeciesReference
stoichiometry: 1.0
species: 575191

576871
type: Reaction
kinetic law: 483249
product: 483237
product: 483225
reactant: 483213
fast: false
reversible: false

274613
type: LocalParameter
units: 479585
value: 7.542E-13

483237
type: SpeciesReference
stoichiometry: 1.0
species: 575071

483225
type: SpeciesReference
stoichiometry: 1.0
species: 574531

483213
type: SpeciesReference
stoichiometry: 1.0
species: 575111

576091
type: Reaction
kinetic law: 481361
product: 481349
reactant: 481337
reactant: 481325
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

481361
type: KineticLaw
local parameters: 274517
local parameters: 274515
notes: k1*PLA2_slash_APC*PLA2_slash_PLA2_star__minus_Ca-k2*PLA2_slash_PLA2_star__minus_Ca_slash_kenz_slash_kenz_cplx

274517
type: LocalParameter
units: 479585
value: 6.0336E-11

274515
type: LocalParameter
units: 479672
value: 3.77097654438E-12

481349
type: SpeciesReference
stoichiometry: 1.0
species: 574311

481337
type: SpeciesReference
stoichiometry: 1.0
species: 574291

481325
type: SpeciesReference
stoichiometry: 1.0
species: 575251

576371
type: Reaction
kinetic law: 482042
product: 482030
reactant: 482018
reactant: 482006
fast: false
reversible: true

482042
type: KineticLaw
local parameters: 274552
local parameters: 274550
notes: k1*Ras_slash_GDP_minus_Ras*Ras_slash_inact_minus_GEF-k2*Ras_slash_inact_minus_GEF_slash_basal_GEF_activity_slash_basal_GEF_activity_cplx

274552
type: LocalParameter
units: 479585
value: 1.0056E-14

274550
type: LocalParameter
units: 479672
value: 1.24438339044E-15

482030
type: SpeciesReference
stoichiometry: 1.0
species: 574671

482018
type: SpeciesReference
stoichiometry: 1.0
species: 574651

482006
type: SpeciesReference
stoichiometry: 1.0
species: 574751

576691
type: Reaction
kinetic law: 482814
product: 482802
reactant: 482790
reactant: 482778
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

482814
type: KineticLaw
local parameters: 274592
local parameters: 274590
notes: k1*MAPK_slash_craf_minus_1_star_*MAPK_star_-k2*MAPK_star__slash_MAPK_star__minus_feedback_slash_MAPK_star__minus_feedback_cplx

274592
type: LocalParameter
units: 479585
value: 5.028E-12

274590
type: LocalParameter
units: 479672
value: 2.45122481664E-13

482802
type: SpeciesReference
stoichiometry: 1.0
species: 574991

482790
type: SpeciesReference
stoichiometry: 1.0
species: 574951

482778
type: SpeciesReference
stoichiometry: 1.0
species: 574371

573971
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851

575851
type: Reaction
kinetic law: 480791
product: 480779
reactant: 480767
reactant: 480755
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

480791
type: KineticLaw
local parameters: 274491
local parameters: 274489
notes: kf*CaM_slash_CaM_minus_TR2_minus_Ca2*Ca-kb*CaM_slash_CaM_minus_Ca3

274491
type: LocalParameter
units: 479585
value: 1.257E-12

274489
type: LocalParameter
units: 479672
value: 4.52522873502E-13

480779
type: SpeciesReference
stoichiometry: 1.0
species: 575191

480767
type: SpeciesReference
stoichiometry: 1.0
species: 574852

480755
type: SpeciesReference
stoichiometry: 1.0
species: 575211

576671
type: Reaction
kinetic law: 482766
product: 482754
product: 482742
reactant: 482730
fast: false
reversible: false

482766
type: KineticLaw
local parameters: 274588
notes: k3*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx

274588
type: LocalParameter
units: 479585
value: 1.257E-12

482754
type: SpeciesReference
stoichiometry: 1.0
species: 574951

482742
type: SpeciesReference
stoichiometry: 1.0
species: 574331

482730
type: SpeciesReference
stoichiometry: 1.0
species: 574971

576411
type: Reaction
kinetic law: 482139
product: 482127
reactant: 482115
reactant: 482103
notes: Kinetics same as GEF-bg-act-ras
fast: false
reversible: true

482139
type: KineticLaw
local parameters: 274557
local parameters: 274555
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

274557
type: LocalParameter
units: 479585
value: 1.0056E-14

274555
type: LocalParameter
units: 479672
value: 2.48886158382E-14

482127
type: SpeciesReference
stoichiometry: 1.0
species: 574711

482115
type: SpeciesReference
stoichiometry: 1.0
species: 574691

482103
type: SpeciesReference
stoichiometry: 1.0
species: 574751

575611
type: Reaction
kinetic law: 480269
product: 480257
reactant: 480245
reactant: 480233
fast: false
reversible: true

480269
type: KineticLaw
local parameters: 274465
local parameters: 274464
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_cytosolic-kb*PLA2_slash_PIP2_minus_PLA2_star_

274465
type: LocalParameter
units: 479585
value: 6.285E-14

274464
type: LocalParameter
units: 479672
value: 1.50840957834E-16

480257
type: SpeciesReference
stoichiometry: 1.0
species: 574171

480245
type: SpeciesReference
stoichiometry: 1.0
species: 574111

480233
type: SpeciesReference
stoichiometry: 1.0
species: 575271

576611
type: Reaction
kinetic law: 482621
product: 482609
reactant: 482597
reactant: 482584
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

482621
type: KineticLaw
local parameters: 274582
local parameters: 274580
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

274582
type: LocalParameter
units: 479585
value: 2.0112E-12

274580
type: LocalParameter
units: 479672
value: 7.5420478917E-13

482609
type: SpeciesReference
stoichiometry: 1.0
species: 574911

482597
type: SpeciesReference
stoichiometry: 1.0
species: 575351

482584
type: SpeciesReference
stoichiometry: 1.0
species: 574651

576271
type: Reaction
kinetic law: 481799
product: 481786
product: 481774
reactant: 481762
fast: false
reversible: false

481799
type: KineticLaw
local parameters: 274538
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

274538
type: LocalParameter
units: 479585
value: 3.771E-14

481786
type: SpeciesReference
stoichiometry: 1.0
species: 574551

481774
type: SpeciesReference
stoichiometry: 1.0
species: 574471

481762
type: SpeciesReference
stoichiometry: 1.0
species: 574571

576131
type: Reaction
kinetic law: 481457
product: 481445
reactant: 481433
reactant: 481421
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

481457
type: KineticLaw
local parameters: 274522
local parameters: 274520
notes: k1*MAPK_slash_MAPK*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx

274522
type: LocalParameter
units: 479585
value: 1.5084E-13

274520
type: LocalParameter
units: 479672
value: 4.07263949946E-12

481445
type: SpeciesReference
stoichiometry: 1.0
species: 574491

481433
type: SpeciesReference
stoichiometry: 1.0
species: 574471

481421
type: SpeciesReference
stoichiometry: 1.0
species: 574411

573839
type: Compartment
constant: true
size: 1.0E-18
spatial dimensions: 3.0

575511
type: Reaction
kinetic law: 480025
product: 480013
reactant: 480001
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

480025
type: KineticLaw
local parameters: 274455
local parameters: 274454
notes: kf*PKC_slash_PKC_minus_cytosolic-kb*PKC_slash_PKC_minus_basal_star_

274455
type: LocalParameter
units: 479585
value: 6.285E-12

274454
type: LocalParameter
units: 479585
value: 1.257E-13

480013
type: SpeciesReference
stoichiometry: 1.0
species: 573971

480001
type: SpeciesReference
stoichiometry: 1.0
species: 574071

576351
type: Reaction
kinetic law: 481993
product: 481980
product: 481968
reactant: 481956
fast: false
reversible: false

481993
type: KineticLaw
local parameters: 274548
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

274548
type: LocalParameter
units: 479585
value: 3.771E-14

481980
type: SpeciesReference
stoichiometry: 1.0
species: 574591

481968
type: SpeciesReference
stoichiometry: 1.0
species: 574471

481956
type: SpeciesReference
stoichiometry: 1.0
species: 574631

575311
type: Species
notes: Peak IP3 is perhaps 15 uM, basal <= 0.2 uM.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.730005303632989
initial amount: NaN
in compartment: 573851

575931
type: Reaction
kinetic law: 480974
product: 480962
reactant: 480950
reactant: 480938
notes: 10 x raise oct22 12 x oct 24, set k2 = 4 * k3
fast: false
reversible: true

480974
type: KineticLaw
local parameters: 274499
local parameters: 274498
notes: k1*PLA2_slash_APC*PLA2_slash_PLA2_minus_Ca_star_-k2*PLA2_slash_PLA2_minus_Ca_star__slash_kenz_slash_kenz_cplx

274499
type: LocalParameter
units: 479585
value: 2.71512E-12

274498
type: LocalParameter
units: 479672
value: 1.696972626E-13

480962
type: SpeciesReference
stoichiometry: 1.0
species: 574151

480950
type: SpeciesReference
stoichiometry: 1.0
species: 574131

480938
type: SpeciesReference
stoichiometry: 1.0
species: 575251

576531
type: Reaction
kinetic law: 482427
product: 482415
reactant: 482403
reactant: 482391
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

482427
type: KineticLaw
local parameters: 274572
local parameters: 274570
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

274572
type: LocalParameter
units: 479585
value: 2.0112E-12

274570
type: LocalParameter
units: 479672
value: 3.77097654438E-14

482415
type: SpeciesReference
stoichiometry: 1.0
species: 574871

482403
type: SpeciesReference
stoichiometry: 1.0
species: 575351

482391
type: SpeciesReference
stoichiometry: 1.0
species: 574351

575671
type: Reaction
kinetic law: 480403
product: 480391
reactant: 480379
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

480403
type: KineticLaw
local parameters: 274472
local parameters: 274471
notes: kf*AA-kb*PLA2_slash_APC

274472
type: LocalParameter
units: 479585
value: 0.0

274471
type: LocalParameter
units: 479585
value: 5.028E-14

480391
type: SpeciesReference
stoichiometry: 1.0
species: 575251

480379
type: SpeciesReference
stoichiometry: 1.0
species: 574091

575731
type: Reaction
kinetic law: 480535
product: 480523
reactant: 480511
reactant: 480499
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

480535
type: KineticLaw
local parameters: 274478
local parameters: 274477
notes: kf*MAPK_slash_craf_minus_1_star_*Ras_slash_GTP_minus_Ras-kb*MAPK_slash_Raf_star__minus_GTP_minus_Ras

274478
type: LocalParameter
units: 479585
value: 6.285E-14

274477
type: LocalParameter
units: 479672
value: 1.25699218146E-12

480523
type: SpeciesReference
stoichiometry: 1.0
species: 574591

480511
type: SpeciesReference
stoichiometry: 1.0
species: 574731

480499
type: SpeciesReference
stoichiometry: 1.0
species: 574371

575391
type: Reaction
kinetic law: 479782
product: 479769
reactant: 479757
reactant: 479745
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

479782
type: KineticLaw
local parameters: 274442
local parameters: 274441
notes: kf*PKC_slash_PKC_minus_cytosolic*Ca-kb*PKC_slash_PKC_minus_Ca

274442
type: LocalParameter
units: 479585
value: 6.285E-14

274441
type: LocalParameter
units: 479672
value: 7.5420478917E-14

479769
type: SpeciesReference
stoichiometry: 1.0
species: 573871

479757
type: SpeciesReference
stoichiometry: 1.0
species: 574852

479745
type: SpeciesReference
stoichiometry: 1.0
species: 574071

576191
type: Reaction
kinetic law: 481604
product: 481592
product: 481580
reactant: 481568
fast: false
reversible: false

481604
type: KineticLaw
local parameters: 274528
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx

274528
type: LocalParameter
units: 479585
value: 3.771E-14

481592
type: SpeciesReference
stoichiometry: 1.0
species: 574471

481580
type: SpeciesReference
stoichiometry: 1.0
species: 574951

481568
type: SpeciesReference
stoichiometry: 1.0
species: 574511

576751
type: Reaction
kinetic law: 482958
product: 482946
product: 482934
reactant: 482922
fast: false
reversible: false

482958
type: KineticLaw
local parameters: 274598
notes: k3*MKP_minus_1_slash_MKP1_minus_tyr_minus_deph_slash_MKP1_minus_tyr_minus_deph_cplx

274598
type: LocalParameter
units: 479585
value: 5.028E-13

482946
type: SpeciesReference
stoichiometry: 1.0
species: 575011

482934
type: SpeciesReference
stoichiometry: 1.0
species: 574411

482922
type: SpeciesReference
stoichiometry: 1.0
species: 575031

576891
type: Reaction
kinetic law: 483297
product: 483285
reactant: 483273
reactant: 483261
fast: false
reversible: true

274617
type: LocalParameter
units: 479585
value: 3.0168E-12

274615
type: LocalParameter
units: 479672
value: 2.40856349364E-13

483285
type: SpeciesReference
stoichiometry: 1.0
species: 575131

483273
type: SpeciesReference
stoichiometry: 1.0
species: 575071

483261
type: SpeciesReference
stoichiometry: 1.0
species: 574531