MODEL9071122126
type: SBMLModel
reaction: 868739
reaction: 869039
reaction: 868679
species: 868001
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species: 867839
reaction: 868459
species: 867499
reaction: 868219
reaction: 869359
reaction: 869119
reaction: 868939
species: 867559
species: 867179
volume units: 679943
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reaction: 868719
is described by: http://identifiers.org/pubmed/9888852
reaction: 869099
reaction: 868899
reaction: 868659
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species: 867180
reaction: 868879
reaction: 869079
reaction: 868639
rule: 868119
reaction: 868499
reaction: 868419
notes: This model is based closely on the one from Bhalla US and Iyengar R. Science (1999) 283(5400):381-7. This is a stripped down version with only the essential components of the feedback loop:PKC, Ras and the MAPK cascade, and PLA2 in the synapse. The upregulation of MKP-1 is not incorporated in this model since it is treated as a fixed regulatory input. This model was used to develop figures 2 - 4 which show the bistable region of parameter space when the regulatory inputs Ca, PP2A and MKP-1 are varied. This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
species: 867799
species: 867459
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reaction: 869319
species: 867979
species: 867939
reaction: 868159
species: 868019
species: 867219
species: 867400
reaction: 869299
reaction: 868859
reaction: 869059
reaction: 868619
reaction: 868180
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species: 867959
species: 867480
reaction: 868599
reaction: 869379
species: 867539
species: 868079
reaction: 868379
species: 867239
reaction: 868139
time units: 131570
species: 867300
species: 867359
reaction: 869279
reaction: 868839
name: Bhalla1999_3d_fold_model
species: 868099
reaction: 868579
species: 867759

868739
type: Reaction
kinetic law: 161327
product: 161315
product: 161303
reactant: 161291
fast: false
reversible: false

161327
type: KineticLaw
local parameters: 259015
notes: k3*MAPK_slash_Raf_minus_GTP_minus_Ras_star__slash_Raf_minus_GTP_minus_Ras_star__dot_1_slash_Raf_minus_GTP_minus_Ras_star__dot_1_cplx

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units: 159727
value: 1.05E-13

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species: 867439

867439
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867160
type: Compartment
constant: true
size: 1.0E-12
spatial dimensions: 3.0

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867440
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869039
type: Reaction
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reactant: 162030
reactant: 162018
fast: false
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units: 159727
value: 2.5E-11

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value: 1.98E-12

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kind: MOLE

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867619
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867559
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initial concentration: 0.224
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162018
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species: 867420

868679
type: Reaction
kinetic law: 161182
product: 161170
reactant: 161158
reactant: 161146
notes: Rate consts same as for MAPKKtyr.
fast: false
reversible: true

161182
type: KineticLaw
local parameters: 259008
local parameters: 259005
notes: k1*MAPK_slash_MAPK_minus_tyr*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx

259008
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units: 159727
value: 6.0E-13

259005
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units: 159763
value: 1.62E-11

161170
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867419
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161158
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species: 867399

867399
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161146
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867380
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initial amount: NaN
in compartment: 867160

868001
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constant: false
boundary condition: false
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initial concentration: 0.0
initial amount: NaN
in compartment: 867160

867879
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in compartment: 867160

867839
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constant: false
boundary condition: false
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initial concentration: 0.0
initial amount: NaN
in compartment: 867160

868459
type: Reaction
kinetic law: 160661
product: 160648
reactant: 160636
fast: false
reversible: true

160661
type: KineticLaw
local parameters: 258981
local parameters: 258980
notes: kf*Ras_slash_GEF_star_-kb*Ras_slash_inact_minus_GEF

258981
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units: 159727
value: 0.0

258980
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value: 1.0E-12

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867899
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867499
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initial concentration: 0.0032
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in compartment: 867160

868219
type: Reaction
kinetic law: 160077
product: 160065
reactant: 160053
notes: Assume slowish too. Schaechter and Benowitz
fast: false
reversible: true

160077
type: KineticLaw
local parameters: 258950
local parameters: 258949
notes: kf*PKC_slash_PKC_minus_DAG_minus_AA-kb*PKC_slash_PKC_minus_DAG_minus_AA_star_

258950
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units: 159727
value: 2.0E-13

258949
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units: 159727
value: 2.0E-12

160065
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867180
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160053
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867279
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in compartment: 867160

869359
type: Reaction
kinetic law: 162829
product: 162817
reactant: 162805
reactant: 162793
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)
fast: false
reversible: true

162829
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local parameters: 259107
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

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units: 159727
value: 1.0E-9

259107
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units: 159763
value: 9.996E-10

162817
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species: 868001

162805
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initial concentration: 0.002
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species: 867939

867939
type: Species
constant: false
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in compartment: 867160

869119
type: Reaction
kinetic law: 162247
product: 162235
reactant: 162223
reactant: 162211
notes: 10 x raise oct22 12 x oct 24, set k2 = 4 * k3
fast: false
reversible: true

162247
type: KineticLaw
local parameters: 259074
local parameters: 259071
notes: k1*PLA2_slash_APC*PLA2_slash_PLA2_minus_Ca_star_-k2*PLA2_slash_PLA2_minus_Ca_star__slash_kenz_slash_kenz_cplx

259074
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units: 159727
value: 2.16E-11

259071
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units: 159763
value: 1.35E-12

162235
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867679
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species: 867660

867660
type: Species
constant: false
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in compartment: 867160

162211
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species: 868059

868059
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
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initial concentration: 30.0
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in compartment: 867160

868939
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fast: false
reversible: false

161813
type: KineticLaw
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notes: k3*MKP_minus_1_slash_MKP1_minus_thr_minus_deph_slash_MKP1_minus_thr_minus_deph_cplx

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species: 867499

161789
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species: 867380

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species: 867539

867539
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in compartment: 867160

867179
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initial concentration: 3.72083333333333E-17
initial amount: NaN
in compartment: 867160

867519
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boundary condition: false
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initial concentration: 0.0
initial amount: NaN
in compartment: 867160

868199
type: Reaction
kinetic law: 160041
product: 160029
reactant: 160017
reactant: 160005
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

160041
type: KineticLaw
local parameters: 258948
local parameters: 258947
notes: kf*PKC_slash_PKC_minus_Ca*AA-kb*PKC_slash_PKC_minus_Ca_minus_AA_star_

258948
type: LocalParameter
units: 159727
value: 1.0E-13

258947
type: LocalParameter
units: 159763
value: 1.2E-15

160029
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species: 867199

867199
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initial concentration: 1.75E-16
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in compartment: 867160

160017
type: SpeciesReference
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species: 867299

867299
type: Species
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initial amount: NaN
in compartment: 867160

160005
type: SpeciesReference
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species: 867179

868719
type: Reaction
kinetic law: 161279
product: 161267
reactant: 161255
reactant: 161243
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

161279
type: KineticLaw
local parameters: 259014
local parameters: 259011
notes: k1*MAPK_slash_MAPKK*MAPK_slash_Raf_minus_GTP_minus_Ras_star_-k2*MAPK_slash_Raf_minus_GTP_minus_Ras_star__slash_Raf_minus_GTP_minus_Ras_star__dot_1_slash_Raf_minus_GTP_minus_Ras_star__dot_1_cplx

259014
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units: 159727
value: 4.2E-13

259011
type: LocalParameter
units: 159763
value: 3.3E-12

161267
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species: 867440

161255
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species: 867439

161243
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species: 867359

867359
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constant: false
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has only substance units: false
initial concentration: 0.18
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in compartment: 867160

869099
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product: 162187
product: 162175
reactant: 162163
fast: false
reversible: false

259069
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units: 159727
value: 6.0E-12

162187
type: SpeciesReference
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species: 867559

162175
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species: 867340

867340
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160

162163
type: SpeciesReference
stoichiometry: 1.0
species: 867639

867639
type: Species
constant: false
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has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160

868899
type: Reaction
kinetic law: 161717
product: 161704
product: 161692
reactant: 161680
fast: false
reversible: false

161717
type: KineticLaw
local parameters: 259039
notes: k3*MKP_minus_1_slash_MKP1_minus_tyr_minus_deph_slash_MKP1_minus_tyr_minus_deph_cplx

259039
type: LocalParameter
units: 159727
value: 1.0E-12

161704
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species: 867499

161692
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species: 867360

867360
type: Species
constant: false
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has only substance units: false
initial concentration: 0.36
initial amount: NaN
in compartment: 867160

161680
type: SpeciesReference
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species: 867519

868659
type: Reaction
kinetic law: 161134
product: 161121
product: 161108
reactant: 161095
fast: false
reversible: false

161134
type: KineticLaw
local parameters: 259003
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx

259003
type: LocalParameter
units: 159727
value: 1.5E-13

161121
type: SpeciesReference
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species: 867399

161108
type: SpeciesReference
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species: 867380

161095
type: SpeciesReference
stoichiometry: 1.0
species: 867400

867400
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160

867320
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constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160

868439
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kinetic law: 160624
product: 160612
reactant: 160600
fast: false
reversible: true

160624
type: KineticLaw
local parameters: 258979
local parameters: 258976
notes: kf*PLA2_slash_PLA2_star_-kb*PLA2_slash_PLA2_minus_cytosolic

258979
type: LocalParameter
units: 159727
value: 0.0

258976
type: LocalParameter
units: 159727
value: 1.7E-13

160612
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species: 867659

867659
type: Species
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initial concentration: 0.4
initial amount: NaN
in compartment: 867160

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type: Species
constant: false
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has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160

868279
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kinetic law: 160261
product: 160248
reactant: 160236
reactant: 160224
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

160261
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local parameters: 258960
local parameters: 258959
notes: kf*PKC_slash_PKC_minus_DAG*AA-kb*PKC_slash_PKC_minus_DAG_minus_AA

258960
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units: 159727
value: 2.0E-12

258959
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units: 159763
value: 1.8E-14

160248
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species: 867279

160236
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species: 867299

160224
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species: 867260

867260
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.16101666666667E-16
initial amount: NaN
in compartment: 867160

867579
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160

869339
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kinetic law: 162781
product: 162769
product: 162757
reactant: 162745
fast: false
reversible: false

162781
type: KineticLaw
local parameters: 259105
notes: k3*Ras_slash_GEF_star__slash_GEF_star__minus_act_minus_ras_slash_GEF_star__minus_act_minus_ras_cplx

259105
type: LocalParameter
units: 159727
value: 2.0E-14

162769
type: SpeciesReference
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species: 867899

162757
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species: 867939

162745
type: SpeciesReference
stoichiometry: 1.0
species: 867919

867919
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160

867779
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160

867739
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160

868179
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kinetic law: 159957
product: 159945
reactant: 159933
fast: false
reversible: true

159957
type: KineticLaw
local parameters: 258944
local parameters: 258943
notes: kf*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_memb_star_

258944
type: LocalParameter
units: 159727
value: 3.5026E-12

258943
type: LocalParameter
units: 159727
value: 1.2705E-12

159945
type: SpeciesReference
stoichiometry: 1.0
species: 867200

867200
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.3896E-17
initial amount: NaN
in compartment: 867160

159933
type: SpeciesReference
stoichiometry: 1.0
species: 867179

868879
type: Reaction
kinetic law: 161668
product: 161656
reactant: 161644
reactant: 161632
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

161668
type: KineticLaw
local parameters: 259038
local parameters: 259035
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

259038
type: LocalParameter
units: 159727
value: 4.0E-12

259035
type: LocalParameter
units: 159763
value: 7.5E-11

161656
type: SpeciesReference
stoichiometry: 1.0
species: 867519

161644
type: SpeciesReference
stoichiometry: 1.0
species: 867499

161632
type: SpeciesReference
stoichiometry: 1.0
species: 867380

869079
type: Reaction
kinetic law: 162151
product: 162139
reactant: 162127
reactant: 162115
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

259068
type: LocalParameter
units: 159727
value: 2.5E-11

259065
type: LocalParameter
units: 159763
value: 1.98E-12

162139
type: SpeciesReference
stoichiometry: 1.0
species: 867639

162127
type: SpeciesReference
stoichiometry: 1.0
species: 867559

162115
type: SpeciesReference
stoichiometry: 1.0
species: 867379

867379
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160

868639
type: Reaction
kinetic law: 161081
product: 161068
reactant: 161055
reactant: 161042
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

161081
type: KineticLaw
local parameters: 259002
local parameters: 258999
notes: k1*MAPK_slash_MAPK*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx

259002
type: LocalParameter
units: 159727
value: 6.0E-13

258999
type: LocalParameter
units: 159763
value: 1.62E-11

161068
type: SpeciesReference
stoichiometry: 1.0
species: 867400

161055
type: SpeciesReference
stoichiometry: 1.0
species: 867399

161042
type: SpeciesReference
stoichiometry: 1.0
species: 867360

868499
type: Reaction
kinetic law: 160735
product: 160723
reactant: 160710
notes: Assume a reasonably good rate for dephosphorylating it, 1/sec
fast: false
reversible: true

160735
type: KineticLaw
local parameters: 258985
local parameters: 258984
notes: kf*Ras_slash_GAP_star_-kb*Ras_slash_GAP

258985
type: LocalParameter
units: 159727
value: 0.0

258984
type: LocalParameter
units: 159727
value: 1.0E-13

160723
type: SpeciesReference
stoichiometry: 1.0
species: 867999

160710
type: SpeciesReference
stoichiometry: 1.0
species: 867979

867979
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160

868419
type: Reaction
kinetic law: 160588
product: 160576
reactant: 160564
reactant: 160552
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

160588
type: KineticLaw
local parameters: 258974
local parameters: 258973
notes: kf*PLA2_slash_PLA2_star_*Ca-kb*PLA2_slash_PLA2_star__minus_Ca

258974
type: LocalParameter
units: 159727
value: 1.0E-13

258973
type: LocalParameter
units: 159763
value: 6.0E-12

160576
type: SpeciesReference
stoichiometry: 1.0
species: 867819

867819
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160

160564
type: SpeciesReference
stoichiometry: 1.0
species: 868039

868039
type: Species
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.08
initial amount: NaN
in compartment: 867160

160552
type: SpeciesReference
stoichiometry: 1.0
species: 867859

867799
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160

867459
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160

869319
type: Reaction
kinetic law: 162733
product: 162721
reactant: 162709
reactant: 162697
notes: Kinetics same as GEF-bg-act-ras
fast: false
reversible: true

162733
type: KineticLaw
local parameters: 259104
local parameters: 259101
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

259104
type: LocalParameter
units: 159727
value: 8.0E-14

259101
type: LocalParameter
units: 159763
value: 1.98E-13

162721
type: SpeciesReference
stoichiometry: 1.0
species: 867919

162709
type: SpeciesReference
stoichiometry: 1.0
species: 867899

162697
type: SpeciesReference
stoichiometry: 1.0
species: 867959

867959
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.2
initial amount: NaN
in compartment: 867160

868159
type: Reaction
kinetic law: 159921
product: 159909
reactant: 159896
reactant: 159884
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

159921
type: KineticLaw
local parameters: 258942
local parameters: 258941
notes: kf*DAG*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_DAG

258942
type: LocalParameter
units: 159727
value: 8.6348E-12

258941
type: LocalParameter
units: 159763
value: 7.9998E-15

159909
type: SpeciesReference
stoichiometry: 1.0
species: 867240

867240
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 8.46316666666667E-23
initial amount: NaN
in compartment: 867160

159896
type: SpeciesReference
stoichiometry: 1.0
species: 867179

159884
type: SpeciesReference
stoichiometry: 1.0
species: 868019

868019
type: Species
notes: Baseline is 11.661 from running combined model to steady state. See ALL/NOTES for 23 Apr 1998.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 11.661
initial amount: NaN
in compartment: 867160

867219
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 9.43516666666667E-21
initial amount: NaN
in compartment: 867160

869299
type: Reaction
kinetic law: 162685
product: 162672
product: 162660
reactant: 162648
fast: false
reversible: false

162685
type: KineticLaw
local parameters: 259099
notes: k3*PLA2_slash_PLA2_star__minus_Ca_slash_kenz_slash_kenz_cplx

259099
type: LocalParameter
units: 159727
value: 1.2E-10

162672
type: SpeciesReference
stoichiometry: 1.0
species: 867819

162660
type: SpeciesReference
stoichiometry: 1.0
species: 867299

162648
type: SpeciesReference
stoichiometry: 1.0
species: 867839

868859
type: Reaction
kinetic law: 161620
product: 161608
product: 161596
reactant: 161583
fast: false
reversible: false

161620
type: KineticLaw
local parameters: 259033
notes: k3*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx

259033
type: LocalParameter
units: 159727
value: 2.0E-11

161608
type: SpeciesReference
stoichiometry: 1.0
species: 867460

867460
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160

161596
type: SpeciesReference
stoichiometry: 1.0
species: 867859

161583
type: SpeciesReference
stoichiometry: 1.0
species: 867480

867480
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160

869059
type: Reaction
kinetic law: 162103
product: 162091
product: 162079
reactant: 162067
fast: false
reversible: false

259063
type: LocalParameter
units: 159727
value: 6.0E-12

162091
type: SpeciesReference
stoichiometry: 1.0
species: 867559

162079
type: SpeciesReference
stoichiometry: 1.0
species: 867359

162067
type: SpeciesReference
stoichiometry: 1.0
species: 867619

868619
type: Reaction
kinetic law: 161029
product: 161016
product: 161003
reactant: 160990
fast: false
reversible: false

161029
type: KineticLaw
local parameters: 258997
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_GEF_slash_PKC_minus_act_minus_GEF_cplx

258997
type: LocalParameter
units: 159727
value: 4.0E-12

161016
type: SpeciesReference
stoichiometry: 1.0
species: 868099

868099
type: Species
constant: false
boundary condition: true
has only substance units: false
initial concentration: 2.12216666666667E-16
initial amount: NaN
in compartment: 867160

161003
type: SpeciesReference
stoichiometry: 1.0
species: 867899

160990
type: SpeciesReference
stoichiometry: 1.0
species: 867320

868180
type: Reaction
kinetic law: 159993
product: 159981
reactant: 159969
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

159993
type: KineticLaw
local parameters: 258946
local parameters: 258945
notes: kf*PKC_slash_PKC_minus_Ca_minus_DAG-kb*PKC_slash_PKC_minus_DAG_minus_memb_star_

258946
type: LocalParameter
units: 159727
value: 1.0E-13

258945
type: LocalParameter
units: 159727
value: 1.0E-12

159981
type: SpeciesReference
stoichiometry: 1.0
species: 867219

159969
type: SpeciesReference
stoichiometry: 1.0
species: 867240

868599
type: Reaction
kinetic law: 160977
product: 160965
reactant: 160953
reactant: 160941
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

160977
type: KineticLaw
local parameters: 258996
local parameters: 258993
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

258996
type: LocalParameter
units: 159727
value: 1.6E-11

258993
type: LocalParameter
units: 159763
value: 6.0E-12

160965
type: SpeciesReference
stoichiometry: 1.0
species: 867320

160953
type: SpeciesReference
stoichiometry: 1.0
species: 868099

160941
type: SpeciesReference
stoichiometry: 1.0
species: 867879

869379
type: Reaction
kinetic law: 162878
product: 162866
product: 162854
reactant: 162841
fast: false
reversible: false

162878
type: KineticLaw
local parameters: 259111
notes: k3*Ras_slash_GAP_slash_GAP_minus_inact_minus_ras_slash_GAP_minus_inact_minus_ras_cplx

259111
type: LocalParameter
units: 159727
value: 1.0E-11

162866
type: SpeciesReference
stoichiometry: 1.0
species: 867999

162854
type: SpeciesReference
stoichiometry: 1.0
species: 867959

162841
type: SpeciesReference
stoichiometry: 1.0
species: 868001

868079
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: 867160

868379
type: Reaction
kinetic law: 160503
product: 160491
reactant: 160479
reactant: 160467
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

160503
type: KineticLaw
local parameters: 258970
local parameters: 258969
notes: kf*DAG*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_DAG_minus_Ca_minus_PLA2_star_

258970
type: LocalParameter
units: 159727
value: 4.0E-12

258969
type: LocalParameter
units: 159763
value: 3.0E-15

160491
type: SpeciesReference
stoichiometry: 1.0
species: 867779

160479
type: SpeciesReference
stoichiometry: 1.0
species: 867660

160467
type: SpeciesReference
stoichiometry: 1.0
species: 868019

867239
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.81333333333333E-17
initial amount: NaN
in compartment: 867160

868139
type: Reaction
kinetic law: 159872
product: 159860
reactant: 159848
reactant: 159835
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

159872
type: KineticLaw
local parameters: 258940
local parameters: 258937
notes: kf*PKC_slash_PKC_minus_cytosolic*Ca-kb*PKC_slash_PKC_minus_Ca

258940
type: LocalParameter
units: 159727
value: 5.0E-13

258937
type: LocalParameter
units: 159763
value: 6.0E-13

159860
type: SpeciesReference
stoichiometry: 1.0
species: 867179

159848
type: SpeciesReference
stoichiometry: 1.0
species: 868039

159835
type: SpeciesReference
stoichiometry: 1.0
species: 867280

867280
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 867160

867300
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160

869279
type: Reaction
kinetic law: 162636
product: 162624
reactant: 162611
reactant: 162599
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

162636
type: KineticLaw
local parameters: 259098
local parameters: 259095
notes: k1*PLA2_slash_APC*PLA2_slash_PLA2_star__minus_Ca-k2*PLA2_slash_PLA2_star__minus_Ca_slash_kenz_slash_kenz_cplx

259098
type: LocalParameter
units: 159727
value: 4.8E-10

259095
type: LocalParameter
units: 159763
value: 3.0E-11

162624
type: SpeciesReference
stoichiometry: 1.0
species: 867839

162611
type: SpeciesReference
stoichiometry: 1.0
species: 867819

162599
type: SpeciesReference
stoichiometry: 1.0
species: 868059

868839
type: Reaction
kinetic law: 161570
product: 161558
reactant: 161546
reactant: 161534
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

161570
type: KineticLaw
local parameters: 259032
local parameters: 259029
notes: k1*PLA2_slash_PLA2_minus_cytosolic*MAPK_star_-k2*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx

259032
type: LocalParameter
units: 159727
value: 8.0E-11

259029
type: LocalParameter
units: 159763
value: 3.9E-12

161558
type: SpeciesReference
stoichiometry: 1.0
species: 867480

161546
type: SpeciesReference
stoichiometry: 1.0
species: 867460

161534
type: SpeciesReference
stoichiometry: 1.0
species: 867659

868579
type: Reaction
kinetic law: 160929
product: 160917
product: 160904
reactant: 160892
fast: false
reversible: false

160929
type: KineticLaw
local parameters: 258991
notes: k3*PKC_minus_active_slash_PKC_minus_inact_minus_GAP_slash_PKC_minus_inact_minus_GAP_cplx

258991
type: LocalParameter
units: 159727
value: 4.0E-12

160917
type: SpeciesReference
stoichiometry: 1.0
species: 868099

160904
type: SpeciesReference
stoichiometry: 1.0
species: 867979

160892
type: SpeciesReference
stoichiometry: 1.0
species: 867319

867319
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160

867759
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160

867719
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160

868359
type: Reaction
kinetic law: 160455
product: 160443
reactant: 160431
reactant: 160419
fast: false
reversible: true

160455
type: KineticLaw
local parameters: 258968
local parameters: 258967
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star_

258968
type: LocalParameter
units: 159727
value: 1.0E-13

258967
type: LocalParameter
units: 159763
value: 1.2E-14

160443
type: SpeciesReference
stoichiometry: 1.0
species: 867739

160431
type: SpeciesReference
stoichiometry: 1.0
species: 867660

160419
type: SpeciesReference
stoichiometry: 1.0
species: 868079

868299
type: Reaction
kinetic law: 160309
product: 160297
reactant: 160285
reactant: 160273
notes: Assume the binding is fast and is 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 4 x to 4 This step needed to memb-anchor and activate Raf: Leevers et al Nature 369 411-414
fast: false
reversible: true

160309
type: KineticLaw
local parameters: 258962
local parameters: 258961
notes: kf*MAPK_slash_craf_minus_1_star_*Ras_slash_GTP_minus_Ras-kb*MAPK_slash_Raf_minus_GTP_minus_Ras_star_

258962
type: LocalParameter
units: 159727
value: 5.0E-13

258961
type: LocalParameter
units: 159763
value: 2.4E-11

160297
type: SpeciesReference
stoichiometry: 1.0
species: 867439

160285
type: SpeciesReference
stoichiometry: 1.0
species: 867939

160273
type: SpeciesReference
stoichiometry: 1.0
species: 867340

159823
type: SBMLUnit
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE

868819
type: Reaction
kinetic law: 161522
product: 161510
product: 161498
reactant: 161486
fast: false
reversible: false

161522
type: KineticLaw
local parameters: 259027
notes: k3*MAPK_star__slash_MAPK_star__minus_feedback_slash_MAPK_star__minus_feedback_cplx

259027
type: LocalParameter
units: 159727
value: 1.0E-11

161510
type: SpeciesReference
stoichiometry: 1.0
species: 867460

161498
type: SpeciesReference
stoichiometry: 1.0
species: 867379

161486
type: SpeciesReference
stoichiometry: 1.0
species: 867479

867479
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160

869199
type: Reaction
kinetic law: 162442
product: 162430
reactant: 162418
reactant: 162406
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

162442
type: KineticLaw
local parameters: 259086
local parameters: 259083
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

259086
type: LocalParameter
units: 159727
value: 1.44E-10

259083
type: LocalParameter
units: 159763
value: 9.0E-12

162430
type: SpeciesReference
stoichiometry: 1.0
species: 867759

162418
type: SpeciesReference
stoichiometry: 1.0
species: 867739

162406
type: SpeciesReference
stoichiometry: 1.0
species: 868059

868799
type: Reaction
kinetic law: 161474
product: 161462
reactant: 161450
reactant: 161438
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

161474
type: KineticLaw
local parameters: 259026
local parameters: 259023
notes: k1*MAPK_slash_craf_minus_1_star_*MAPK_star_-k2*MAPK_star__slash_MAPK_star__minus_feedback_slash_MAPK_star__minus_feedback_cplx

259026
type: LocalParameter
units: 159727
value: 4.0E-11

259023
type: LocalParameter
units: 159763
value: 1.95E-12

161462
type: SpeciesReference
stoichiometry: 1.0
species: 867479

161450
type: SpeciesReference
stoichiometry: 1.0
species: 867460

161438
type: SpeciesReference
stoichiometry: 1.0
species: 867340

868559
type: Reaction
kinetic law: 160880
product: 160868
reactant: 160856
reactant: 160844
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

160880
type: KineticLaw
local parameters: 258990
local parameters: 258989
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

258990
type: LocalParameter
units: 159727
value: 1.6E-11

258989
type: LocalParameter
units: 159763
value: 6.0E-12

160868
type: SpeciesReference
stoichiometry: 1.0
species: 867319

160856
type: SpeciesReference
stoichiometry: 1.0
species: 868099

160844
type: SpeciesReference
stoichiometry: 1.0
species: 867999

868339
type: Reaction
kinetic law: 160406
product: 160394
reactant: 160382
reactant: 160370
fast: false
reversible: true

160406
type: KineticLaw
local parameters: 258966
local parameters: 258965
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_cytosolic-kb*PLA2_slash_PIP2_minus_PLA2_star_

258966
type: LocalParameter
units: 159727
value: 5.0E-13

258965
type: LocalParameter
units: 159763
value: 1.2E-15

160394
type: SpeciesReference
stoichiometry: 1.0
species: 867699

867699
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160

160382
type: SpeciesReference
stoichiometry: 1.0
species: 867659

160370
type: SpeciesReference
stoichiometry: 1.0
species: 868079

868220
type: Reaction
kinetic law: 160113
product: 160101
reactant: 160089
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

160113
type: KineticLaw
local parameters: 258952
local parameters: 258951
notes: kf*PKC_slash_PKC_minus_cytosolic-kb*PKC_slash_PKC_minus_basal_star_

258952
type: LocalParameter
units: 159727
value: 5.0E-11

258951
type: LocalParameter
units: 159727
value: 1.0E-12

160101
type: SpeciesReference
stoichiometry: 1.0
species: 867220

867220
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.02
initial amount: NaN
in compartment: 867160

160089
type: SpeciesReference
stoichiometry: 1.0
species: 867280

869259
type: Reaction
kinetic law: 162587
product: 162575
product: 162562
reactant: 162550
fast: false
reversible: false

162587
type: KineticLaw
local parameters: 259093
notes: k3*PLA2_slash_DAG_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx

259093
type: LocalParameter
units: 159727
value: 6.0E-11

162575
type: SpeciesReference
stoichiometry: 1.0
species: 867779

162562
type: SpeciesReference
stoichiometry: 1.0
species: 867299

162550
type: SpeciesReference
stoichiometry: 1.0
species: 867799

869019
type: Reaction
kinetic law: 162006
product: 161994
product: 161982
reactant: 161970
fast: false
reversible: false

259057
type: LocalParameter
units: 159727
value: 6.0E-12

161994
type: SpeciesReference
stoichiometry: 1.0
species: 867559

161982
type: SpeciesReference
stoichiometry: 1.0
species: 867420

161970
type: SpeciesReference
stoichiometry: 1.0
species: 867599

867599
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160

869179
type: Reaction
kinetic law: 162394
product: 162382
product: 162370
reactant: 162358
fast: false
reversible: false

162394
type: KineticLaw
local parameters: 259081
notes: k3*PLA2_slash_PIP2_minus_PLA2_star__slash_kenz_slash_kenz_cplx

259081
type: LocalParameter
units: 159727
value: 1.104E-11

162382
type: SpeciesReference
stoichiometry: 1.0
species: 867699

162370
type: SpeciesReference
stoichiometry: 1.0
species: 867299

162358
type: SpeciesReference
stoichiometry: 1.0
species: 867719

868999
type: Reaction
kinetic law: 161957
product: 161945
reactant: 161933
reactant: 161921
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

259056
type: LocalParameter
units: 159727
value: 2.5E-11

259053
type: LocalParameter
units: 159763
value: 1.98E-12

161945
type: SpeciesReference
stoichiometry: 1.0
species: 867599

161933
type: SpeciesReference
stoichiometry: 1.0
species: 867559

161921
type: SpeciesReference
stoichiometry: 1.0
species: 867399

867142
type: Compartment
constant: true
size: 1.0E-18
spatial dimensions: 3.0

868779
type: Reaction
kinetic law: 161426
product: 161414
product: 161402
reactant: 161390
fast: false
reversible: false

161426
type: KineticLaw
local parameters: 259021
notes: k3*MAPK_slash_Raf_minus_GTP_minus_Ras_star__slash_Raf_minus_GTP_minus_Ras_star__dot_2_slash_Raf_minus_GTP_minus_Ras_star__dot_2_cplx

259021
type: LocalParameter
units: 159727
value: 1.05E-13

161414
type: SpeciesReference
stoichiometry: 1.0
species: 867439

161402
type: SpeciesReference
stoichiometry: 1.0
species: 867399

161390
type: SpeciesReference
stoichiometry: 1.0
species: 867459

868539
type: Reaction
kinetic law: 160831
product: 160819
product: 160807
reactant: 160795
fast: false
reversible: false

160831
type: KineticLaw
local parameters: 258988
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_raf_slash_PKC_minus_act_minus_raf_cplx

258988
type: LocalParameter
units: 159727
value: 4.0E-12

160819
type: SpeciesReference
stoichiometry: 1.0
species: 868099

160807
type: SpeciesReference
stoichiometry: 1.0
species: 867340

160795
type: SpeciesReference
stoichiometry: 1.0
species: 867300

868399
type: Reaction
kinetic law: 160540
product: 160527
reactant: 160515
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

160540
type: KineticLaw
local parameters: 258972
local parameters: 258971
notes: kf*AA-kb*PLA2_slash_APC

258972
type: LocalParameter
units: 159727
value: 0.0

258971
type: LocalParameter
units: 159727
value: 4.0E-13

160527
type: SpeciesReference
stoichiometry: 1.0
species: 868059

160515
type: SpeciesReference
stoichiometry: 1.0
species: 867299

868919
type: Reaction
kinetic law: 161765
product: 161753
reactant: 161741
reactant: 161729
notes: See MKP1-tyr-deph
fast: false
reversible: true

161765
type: KineticLaw
local parameters: 259044
local parameters: 259041
notes: k1*MAPK_star_*MKP_minus_1-k2*MKP_minus_1_slash_MKP1_minus_thr_minus_deph_slash_MKP1_minus_thr_minus_deph_cplx

259044
type: LocalParameter
units: 159727
value: 4.0E-12

259041
type: LocalParameter
units: 159763
value: 7.5E-11

161753
type: SpeciesReference
stoichiometry: 1.0
species: 867539

161741
type: SpeciesReference
stoichiometry: 1.0
species: 867499

161729
type: SpeciesReference
stoichiometry: 1.0
species: 867460

868319
type: Reaction
kinetic law: 160358
product: 160346
reactant: 160334
reactant: 160322
notes: Leslie and Channon BBA 1045 (1990) 261-270 fig6 pp267.
fast: false
reversible: true

160358
type: KineticLaw
local parameters: 258964
local parameters: 258963
notes: kf*PLA2_slash_PLA2_minus_cytosolic*Ca-kb*PLA2_slash_PLA2_minus_Ca_star_

258964
type: LocalParameter
units: 159727
value: 1.0E-13

258963
type: LocalParameter
units: 159763
value: 1.00002E-12

160346
type: SpeciesReference
stoichiometry: 1.0
species: 867660

160334
type: SpeciesReference
stoichiometry: 1.0
species: 868039

160322
type: SpeciesReference
stoichiometry: 1.0
species: 867659

867339
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.2
initial amount: NaN
in compartment: 867160

868259
type: Reaction
kinetic law: 160212
product: 160199
reactant: 160187
reactant: 160175
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

160212
type: KineticLaw
local parameters: 258958
local parameters: 258955
notes: kf*PKC_slash_PKC_minus_cytosolic*DAG-kb*PKC_slash_PKC_minus_DAG

258958
type: LocalParameter
units: 159727
value: 1.0E-13

258955
type: LocalParameter
units: 159763
value: 6.0E-16

160199
type: SpeciesReference
stoichiometry: 1.0
species: 867260

160187
type: SpeciesReference
stoichiometry: 1.0
species: 868019

160175
type: SpeciesReference
stoichiometry: 1.0
species: 867280

869239
type: Reaction
kinetic law: 162538
product: 162526
reactant: 162514
reactant: 162502
notes: 10 X raise oct 22 12 X raise oct 24 + conversion to k2 =4 * k3
fast: false
reversible: true

162538
type: KineticLaw
local parameters: 259092
local parameters: 259089
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

259092
type: LocalParameter
units: 159727
value: 2.4E-10

259089
type: LocalParameter
units: 159763
value: 1.5E-11

162526
type: SpeciesReference
stoichiometry: 1.0
species: 867799

162514
type: SpeciesReference
stoichiometry: 1.0
species: 867779

162502
type: SpeciesReference
stoichiometry: 1.0
species: 868059

868979
type: Reaction
kinetic law: 161909
product: 161897
product: 161885
reactant: 161873
fast: false
reversible: false

259051
type: LocalParameter
units: 159727
value: 6.0E-12

161897
type: SpeciesReference
stoichiometry: 1.0
species: 867559

161885
type: SpeciesReference
stoichiometry: 1.0
species: 867339

161873
type: SpeciesReference
stoichiometry: 1.0
species: 867579

869159
type: Reaction
kinetic law: 162345
product: 162332
reactant: 162320
reactant: 162308
notes: 10 X raise oct 22 12 X further raise oct 24 to allow for correct conc of enzyme
fast: false
reversible: true

162345
type: KineticLaw
local parameters: 259080
local parameters: 259077
notes: k1*PLA2_slash_APC*PLA2_slash_PIP2_minus_PLA2_star_-k2*PLA2_slash_PIP2_minus_PLA2_star__slash_kenz_slash_kenz_cplx

259080
type: LocalParameter
units: 159727
value: 4.416E-11

259077
type: LocalParameter
units: 159763
value: 2.76E-12

162332
type: SpeciesReference
stoichiometry: 1.0
species: 867719

162320
type: SpeciesReference
stoichiometry: 1.0
species: 867699

162308
type: SpeciesReference
stoichiometry: 1.0
species: 868059

869219
type: Reaction
kinetic law: 162490
product: 162478
product: 162466
reactant: 162454
fast: false
reversible: false

162490
type: KineticLaw
local parameters: 259087
notes: k3*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx

259087
type: LocalParameter
units: 159727
value: 3.6E-11

162478
type: SpeciesReference
stoichiometry: 1.0
species: 867739

162466
type: SpeciesReference
stoichiometry: 1.0
species: 867299

162454
type: SpeciesReference
stoichiometry: 1.0
species: 867759

868759
type: Reaction
kinetic law: 161378
product: 161365
reactant: 161352
reactant: 161339
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

161378
type: KineticLaw
local parameters: 259020
local parameters: 259017
notes: k1*MAPK_slash_MAPKK_minus_ser*MAPK_slash_Raf_minus_GTP_minus_Ras_star_-k2*MAPK_slash_Raf_minus_GTP_minus_Ras_star__slash_Raf_minus_GTP_minus_Ras_star__dot_2_slash_Raf_minus_GTP_minus_Ras_star__dot_2_cplx

259020
type: LocalParameter
units: 159727
value: 4.2E-13

259017
type: LocalParameter
units: 159763
value: 3.3E-12

161365
type: SpeciesReference
stoichiometry: 1.0
species: 867459

161352
type: SpeciesReference
stoichiometry: 1.0
species: 867439

161339
type: SpeciesReference
stoichiometry: 1.0
species: 867420

868519
type: Reaction
kinetic law: 160783
product: 160771
reactant: 160759
reactant: 160747
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

160783
type: KineticLaw
local parameters: 258987
local parameters: 258986
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

258987
type: LocalParameter
units: 159727
value: 1.6E-11

258986
type: LocalParameter
units: 159763
value: 3.0E-13

160771
type: SpeciesReference
stoichiometry: 1.0
species: 867300

160759
type: SpeciesReference
stoichiometry: 1.0
species: 868099

160747
type: SpeciesReference
stoichiometry: 1.0
species: 867339

868699
type: Reaction
kinetic law: 161231
product: 161219
product: 161207
reactant: 161194
fast: false
reversible: false

161231
type: KineticLaw
local parameters: 259009
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx

259009
type: LocalParameter
units: 159727
value: 1.5E-13

161219
type: SpeciesReference
stoichiometry: 1.0
species: 867399

161207
type: SpeciesReference
stoichiometry: 1.0
species: 867460

161194
type: SpeciesReference
stoichiometry: 1.0
species: 867419

868479
type: Reaction
kinetic law: 160698
product: 160685
reactant: 160673
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

160698
type: KineticLaw
local parameters: 258983
local parameters: 258982
notes: kf*Ras_slash_GTP_minus_Ras-kb*Ras_slash_GDP_minus_Ras

258983
type: LocalParameter
units: 159727
value: 0.0

258982
type: LocalParameter
units: 159727
value: 1.0E-16

160685
type: SpeciesReference
stoichiometry: 1.0
species: 867959

160673
type: SpeciesReference
stoichiometry: 1.0
species: 867939

868239
type: Reaction
kinetic law: 160162
product: 160149
reactant: 160137
reactant: 160125
notes: Raise kf from 1.667e-10 to 2e-10 to get better match to data.
fast: false
reversible: true

160162
type: KineticLaw
local parameters: 258954
local parameters: 258953
notes: kf*AA*PKC_slash_PKC_minus_cytosolic-kb*PKC_slash_PKC_minus_AA_star_

258954
type: LocalParameter
units: 159727
value: 1.0E-13

258953
type: LocalParameter
units: 159763
value: 1.2E-16

160149
type: SpeciesReference
stoichiometry: 1.0
species: 867239

160137
type: SpeciesReference
stoichiometry: 1.0
species: 867280

160125
type: SpeciesReference
stoichiometry: 1.0
species: 867299

869139
type: Reaction
kinetic law: 162296
product: 162283
product: 162271
reactant: 162259
fast: false
reversible: false

162296
type: KineticLaw
local parameters: 259075
notes: k3*PLA2_slash_PLA2_minus_Ca_star__slash_kenz_slash_kenz_cplx

259075
type: LocalParameter
units: 159727
value: 5.4E-12

162283
type: SpeciesReference
stoichiometry: 1.0
species: 867660

162271
type: SpeciesReference
stoichiometry: 1.0
species: 867299

162259
type: SpeciesReference
stoichiometry: 1.0
species: 867679

868959
type: Reaction
kinetic law: 161861
product: 161849
reactant: 161837
reactant: 161825
notes: See parent PPhosphatase2A for parms
fast: false
reversible: true

259050
type: LocalParameter
units: 159727
value: 2.5E-11

259047
type: LocalParameter
units: 159763
value: 1.98E-12

161849
type: SpeciesReference
stoichiometry: 1.0
species: 867579

161837
type: SpeciesReference
stoichiometry: 1.0
species: 867559

161825
type: SpeciesReference
stoichiometry: 1.0
species: 867340