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volume units: 679943
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reaction: 563372
reaction: 563312
species: 562453
reaction: 563513
reaction: 564012
name: Ajay_Bhalla_2007_PKM
species: 561973
reaction: 563053
reaction: 564112
species: 562093
species: 562113
reaction: 564092
species: 562233
compartment: 561833
units def: 491513
species: 561913
species: 562333
species: 562033
reaction: 563892
reaction: 562972
species: 562712
is described by: http://identifiers.org/pubmed/19404460
species: 562493
species: 562892
units def: 491549
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reaction: 563452
notes: This is a non-bistable model of ERKII signaling that also incorporates PKM synthesis triggered by Ca influx. It is a simplified variant of the model of 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: 562752
reaction: 563552
compartment: 561853
species: 562153
reaction: 563672
reaction: 563612
species: 562832
species: 562373
reaction: 563852
reaction: 563912
species: 562273
reaction: 563772
species: 562013
reaction: 562993
reaction: 564152
species: 562632
reaction: 563052
species: 562872
area units: area
reaction: 563112
species: 561893
length unit: length
reaction: 563272
reaction: 563332
species: 562572
reaction: 563412
reaction: 563572
species: 562792
substance units: 491597
curated: false
reaction: 563632
species: 561993
reaction: 563872
species: 562413
reaction: 563792
reaction: 563732
reaction: 563972
reaction: 563192
species: 561933
reaction: 563013
species: 562512
species: 562053
reaction: 563292

562353
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constant: false
boundary condition: false
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initial concentration: 0.0
initial amount: NaN
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561853
type: Compartment
constant: true
size: 1.5E-15
spatial dimensions: 3.0

563212
type: Reaction
kinetic law: 492311
product: 492299
reactant: 492287
notes: Time-course of 2 hours.
fast: false
reversible: true

492311
type: KineticLaw
local parameters: 172962
local parameters: 172961
notes: kf*PKC_slash_PKM_minus_zeta-kb*PKM_slash_degraded_PKM

172962
type: LocalParameter
units: 491513
value: 0.0

491537
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND

491525
type: SBMLUnit
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE

172961
type: LocalParameter
units: 491513
value: 6.285E-17

492299
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species: 562892

562892
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constant: true
boundary condition: true
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492287
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562812
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constant: false
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563152
type: Reaction
kinetic law: 492179
product: 492167
reactant: 492155
reactant: 492143
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

492179
type: KineticLaw
local parameters: 172954
local parameters: 172952
notes: kf*CaM_slash_CaM_minus_Ca2*Ca-kb*CaM_slash_CaM_minus_Ca3

172954
type: LocalParameter
units: 491513
value: 1.257E-12

172952
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units: 491549
value: 4.52522873502E-13

491585
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exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND

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scale: -6
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scale: 0
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562672
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492155
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562732
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constant: false
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initial concentration: 0.08
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492143
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species: 562692

562692
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constant: false
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564072
type: Reaction
kinetic law: 494369
product: 494357
product: 494345
reactant: 494333
fast: false
reversible: false

494369
type: KineticLaw
local parameters: 173038
notes: k3*Ras_slash_CaM_minus_GEF_slash_CaM_minus_GEF_minus_act_minus_ras_slash_CaM_minus_GEF_minus_act_minus_ras_cplx

173038
type: LocalParameter
units: 491513
value: 2.514E-14

494357
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species: 562632

562632
type: Species
constant: false
boundary condition: false
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initial concentration: 0.0
initial amount: NaN
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494345
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species: 562573

562573
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constant: false
boundary condition: false
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494333
type: SpeciesReference
stoichiometry: 1.0
species: 562633

562633
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853

562593
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constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853

563372
type: Reaction
kinetic law: 492675
product: 492663
reactant: 492650
reactant: 492638
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

492675
type: KineticLaw
local parameters: 172982
local parameters: 172981
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

172982
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units: 491513
value: 2.0112E-12

172981
type: LocalParameter
units: 491549
value: 7.5420478917E-13

492663
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562053
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492650
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species: 562932

562932
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constant: false
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initial amount: NaN
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492638
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species: 562532

562532
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constant: false
boundary condition: false
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563312
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kinetic law: 492528
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product: 492504
reactant: 492492
fast: false
reversible: false

492528
type: KineticLaw
local parameters: 172976
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_raf_slash_PKC_minus_act_minus_raf_cplx

172976
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units: 491513
value: 5.028E-13

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492504
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562013
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562453
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constant: false
boundary condition: false
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initial amount: NaN
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563513
type: Reaction
kinetic law: 493016
product: 493004
product: 492991
reactant: 492979
fast: false
reversible: false

493016
type: KineticLaw
local parameters: 172992
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx

172992
type: LocalParameter
units: 491513
value: 3.771E-14

493004
type: SpeciesReference
stoichiometry: 1.0
species: 562233

562233
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
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492991
type: SpeciesReference
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species: 562073

562073
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constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
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stoichiometry: 1.0
species: 562273

562273
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
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564012
type: Reaction
kinetic law: 494225
product: 494213
reactant: 494201
reactant: 494189
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

494225
type: KineticLaw
local parameters: 173034
local parameters: 173032
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

173034
type: LocalParameter
units: 491513
value: 5.028E-12

173032
type: LocalParameter
units: 491549
value: 6.22030530222E-12

494213
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stoichiometry: 1.0
species: 562613

562613
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constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853

494201
type: SpeciesReference
stoichiometry: 1.0
species: 562612

562612
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.01
initial amount: NaN
in compartment: 561853

494189
type: SpeciesReference
stoichiometry: 1.0
species: 562573

561973
type: Species
constant: false
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has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 561853

563053
type: Reaction
kinetic law: 491913
product: 491901
reactant: 491889
fast: false
reversible: true

491913
type: KineticLaw
local parameters: 172936
local parameters: 172934
notes: kf*Ras_slash_GEF_star_-kb*Ras_slash_inact_minus_GEF

172936
type: LocalParameter
units: 491513
value: 0.0

172934
type: LocalParameter
units: 491513
value: 1.257E-13

491901
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species: 562532

491889
type: SpeciesReference
stoichiometry: 1.0
species: 562553

562553
type: Species
constant: false
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has only substance units: false
initial concentration: 0.0
initial amount: NaN
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564112
type: Reaction
kinetic law: 494466
product: 494454
product: 494442
reactant: 494430
fast: false
reversible: false

494466
type: KineticLaw
local parameters: 173041
notes: k3*PKM_slash_PKM_synthesis_slash_kenz_slash_kenz_cplx

173041
type: LocalParameter
units: 491513
value: 6.285E-15

494454
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species: 562772

562772
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boundary condition: false
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initial concentration: 0.001
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species: 561993

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species: 562792

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constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
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562113
type: Species
constant: false
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has only substance units: false
initial concentration: 0.5
initial amount: NaN
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564092
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kinetic law: 494418
product: 494405
reactant: 494393
reactant: 494381
fast: false
reversible: true

494418
type: KineticLaw
local parameters: 173040
local parameters: 173039
notes: k1*PKM_slash_AA_pool*PKM_slash_PKM_synthesis-k2*PKM_slash_PKM_synthesis_slash_kenz_slash_kenz_cplx

173040
type: LocalParameter
units: 491513
value: 2.514E-14

173039
type: LocalParameter
units: 491549
value: 3.14252785512E-15

494405
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species: 562792

494393
type: SpeciesReference
stoichiometry: 1.0
species: 562772

494381
type: SpeciesReference
stoichiometry: 1.0
species: 562872

562872
type: Species
notes: Amino acid pool for synthesis.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 561853

561833
type: Compartment
constant: true
size: 1.0E-18
spatial dimensions: 3.0

561913
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 9.4351630867144E-21
initial amount: NaN
in compartment: 561853

562333
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853

562033
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853

563892
type: Reaction
kinetic law: 493935
product: 493923
reactant: 493911
reactant: 493899
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

173024
type: LocalParameter
units: 491513
value: 3.0168E-12

173023
type: LocalParameter
units: 491549
value: 2.40856349364E-13

493923
type: SpeciesReference
stoichiometry: 1.0
species: 562513

562513
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853

493911
type: SpeciesReference
stoichiometry: 1.0
species: 562472

562472
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 561853

493899
type: SpeciesReference
stoichiometry: 1.0
species: 562193

562193
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853

562972
type: Reaction
kinetic law: 491659
product: 491647
reactant: 491635
reactant: 491622
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

491659
type: KineticLaw
local parameters: 172918
local parameters: 172916
notes: kf*PKC_slash_PKC_minus_cytosolic*Ca-kb*PKC_slash_PKC_minus_Ca

172918
type: LocalParameter
units: 491513
value: 6.285E-14

172916
type: LocalParameter
units: 491549
value: 7.5420478917E-14

491647
type: SpeciesReference
stoichiometry: 1.0
species: 561873

561873
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.72076372315036E-17
initial amount: NaN
in compartment: 561853

491635
type: SpeciesReference
stoichiometry: 1.0
species: 562732

491622
type: SpeciesReference
stoichiometry: 1.0
species: 561973

562712
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853

562493
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853

563452
type: Reaction
kinetic law: 492869
product: 492856
reactant: 492844
reactant: 492832
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

492869
type: KineticLaw
local parameters: 172988
local parameters: 172987
notes: k1*MAPK_slash_MAPK*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx

172988
type: LocalParameter
units: 491513
value: 1.5084E-13

172987
type: LocalParameter
units: 491549
value: 4.07263949946E-12

492856
type: SpeciesReference
stoichiometry: 1.0
species: 562253

492844
type: SpeciesReference
stoichiometry: 1.0
species: 562233

492832
type: SpeciesReference
stoichiometry: 1.0
species: 562173

562173
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.59997348183506
initial amount: NaN
in compartment: 561853

562752
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 561853

563552
type: Reaction
kinetic law: 493112
product: 493100
product: 493088
reactant: 493076
fast: false
reversible: false

493112
type: KineticLaw
local parameters: 172995
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

172995
type: LocalParameter
units: 491513
value: 3.771E-14

493100
type: SpeciesReference
stoichiometry: 1.0
species: 562313

562313
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853

493088
type: SpeciesReference
stoichiometry: 1.0
species: 562293

562293
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853

493076
type: SpeciesReference
stoichiometry: 1.0
species: 562333

562153
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 561853

563672
type: Reaction
kinetic law: 493404
product: 493392
product: 493380
reactant: 493368
fast: false
reversible: false

493404
type: KineticLaw
local parameters: 173006
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

173006
type: LocalParameter
units: 491513
value: 3.771E-14

493392
type: SpeciesReference
stoichiometry: 1.0
species: 562373

562373
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853

493380
type: SpeciesReference
stoichiometry: 1.0
species: 562233

493368
type: SpeciesReference
stoichiometry: 1.0
species: 562413

562413
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853

563612
type: Reaction
kinetic law: 493258
product: 493246
reactant: 493234
reactant: 493222
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

493258
type: KineticLaw
local parameters: 173001
local parameters: 172999
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

173001
type: LocalParameter
units: 491513
value: 1.5084E-13

172999
type: LocalParameter
units: 491549
value: 1.18513155294E-12

493246
type: SpeciesReference
stoichiometry: 1.0
species: 562393

562393
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853

493234
type: SpeciesReference
stoichiometry: 1.0
species: 562373

493222
type: SpeciesReference
stoichiometry: 1.0
species: 562153

562832
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.2
initial amount: NaN
in compartment: 561853

563852
type: Reaction
kinetic law: 493838
product: 493826
reactant: 493814
reactant: 493802
fast: false
reversible: true

173021
type: LocalParameter
units: 491513
value: 3.0168E-12

173019
type: LocalParameter
units: 491549
value: 2.40856349364E-13

493826
type: SpeciesReference
stoichiometry: 1.0
species: 562512

562512
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853

493814
type: SpeciesReference
stoichiometry: 1.0
species: 562472

493802
type: SpeciesReference
stoichiometry: 1.0
species: 562293

563912
type: Reaction
kinetic law: 493983
product: 493971
product: 493959
reactant: 493947
fast: false
reversible: false

173025
type: LocalParameter
units: 491513
value: 7.542E-13

493971
type: SpeciesReference
stoichiometry: 1.0
species: 562472

493959
type: SpeciesReference
stoichiometry: 1.0
species: 562133

493947
type: SpeciesReference
stoichiometry: 1.0
species: 562513

563772
type: Reaction
kinetic law: 493646
product: 493634
reactant: 493622
reactant: 493610
notes: See parent PPhosphatase2A for parms
fast: false
reversible: true

173014
type: LocalParameter
units: 491513
value: 3.0168E-12

173013
type: LocalParameter
units: 491549
value: 2.40856349364E-13

493634
type: SpeciesReference
stoichiometry: 1.0
species: 562473

562473
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853

493622
type: SpeciesReference
stoichiometry: 1.0
species: 562472

493610
type: SpeciesReference
stoichiometry: 1.0
species: 562133

562993
type: Reaction
kinetic law: 491707
product: 491695
reactant: 491683
reactant: 491671
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

491707
type: KineticLaw
local parameters: 172921
local parameters: 172919
notes: kf*DAG*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_DAG

172921
type: LocalParameter
units: 491513
value: 1.08539436E-12

172919
type: LocalParameter
units: 491549
value: 1.00557478458E-15

491695
type: SpeciesReference
stoichiometry: 1.0
species: 561933

561933
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 8.46313975072925E-23
initial amount: NaN
in compartment: 561853

491683
type: SpeciesReference
stoichiometry: 1.0
species: 561873

491671
type: SpeciesReference
stoichiometry: 1.0
species: 562852

562852
type: Species
constant: true
boundary condition: true
has only substance units: false
initial concentration: 12.1999469636701
initial amount: NaN
in compartment: 561853

564152
type: Reaction
kinetic law: 494564
product: 494551
product: 494539
reactant: 494527
fast: false
reversible: false

494564
type: KineticLaw
local parameters: 173045
notes: k3*PKM_slash_Ca_dot_detector_complex_slash_kenz_slash_kenz_cplx

173045
type: LocalParameter
units: 491513
value: 2.514E-14

494551
type: SpeciesReference
stoichiometry: 1.0
species: 562793

562793
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853

494539
type: SpeciesReference
stoichiometry: 1.0
species: 562772

494527
type: SpeciesReference
stoichiometry: 1.0
species: 562812

563052
type: Reaction
kinetic law: 491877
product: 491865
reactant: 491853
reactant: 491841
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

491877
type: KineticLaw
local parameters: 172933
local parameters: 172931
notes: kf*MAPK_slash_craf_minus_1_star_*Ras_slash_GTP_minus_Ras-kb*MAPK_slash_Raf_star__minus_GTP_minus_Ras

172933
type: LocalParameter
units: 491513
value: 6.285E-14

172931
type: LocalParameter
units: 491549
value: 1.25699218146E-12

491865
type: SpeciesReference
stoichiometry: 1.0
species: 562373

491853
type: SpeciesReference
stoichiometry: 1.0
species: 562573

491841
type: SpeciesReference
stoichiometry: 1.0
species: 562133

563112
type: Reaction
kinetic law: 492034
product: 492022
reactant: 492010
reactant: 491998
notes: We have no numbers for this. It is probably between the two extremes represented by the CaMKII phosph states, and I have used guesses based on this. kf=1e-4 kb=1 The reaction is based on Farnsworth et al Nature 376 524-527 1995
fast: false
reversible: true

492034
type: KineticLaw
local parameters: 172945
local parameters: 172943
notes: kf*Ras_slash_inact_minus_GEF*CaM_slash_CaM_minus_Ca4-kb*Ras_slash_CaM_minus_GEF

172945
type: LocalParameter
units: 491513
value: 1.257E-13

172943
type: LocalParameter
units: 491549
value: 2.51398436292E-11

492022
type: SpeciesReference
stoichiometry: 1.0
species: 562632

492010
type: SpeciesReference
stoichiometry: 1.0
species: 562673

562673
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853

491998
type: SpeciesReference
stoichiometry: 1.0
species: 562532

561893
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.38955184301246E-17
initial amount: NaN
in compartment: 561853

563272
type: Reaction
kinetic law: 492432
product: 492420
reactant: 492408
fast: false
reversible: true

492432
type: KineticLaw
local parameters: 172971
local parameters: 172970
notes: kf*Ca_input-kb*Ca

172971
type: LocalParameter
units: 491513
value: 6.285E-13

172970
type: LocalParameter
units: 491513
value: 6.285E-13

492420
type: SpeciesReference
stoichiometry: 1.0
species: 562732

492408
type: SpeciesReference
stoichiometry: 1.0
species: 562912

562912
type: Species
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.08
initial amount: NaN
in compartment: 561853

563332
type: Reaction
kinetic law: 492577
product: 492564
reactant: 492552
reactant: 492540
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

492577
type: KineticLaw
local parameters: 172979
local parameters: 172977
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

172979
type: LocalParameter
units: 491513
value: 2.0112E-12

172977
type: LocalParameter
units: 491549
value: 7.5420478917E-13

492564
type: SpeciesReference
stoichiometry: 1.0
species: 562033

492552
type: SpeciesReference
stoichiometry: 1.0
species: 562932

492540
type: SpeciesReference
stoichiometry: 1.0
species: 562612

562572
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853

563412
type: Reaction
kinetic law: 492772
product: 492760
reactant: 492748
reactant: 492735
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

492772
type: KineticLaw
local parameters: 172985
local parameters: 172984
notes: k1*MAPK_slash_craf_minus_1_star_*MAPK_star_-k2*MAPK_star__slash_MAPK_star__minus_feedback_slash_MAPK_star__minus_feedback_cplx

172985
type: LocalParameter
units: 491513
value: 5.028E-12

172984
type: LocalParameter
units: 491549
value: 2.45122481664E-13

492760
type: SpeciesReference
stoichiometry: 1.0
species: 562093

492748
type: SpeciesReference
stoichiometry: 1.0
species: 562073

492735
type: SpeciesReference
stoichiometry: 1.0
species: 562133

563572
type: Reaction
kinetic law: 493161
product: 493149
reactant: 493136
reactant: 493124
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

493161
type: KineticLaw
local parameters: 172997
local parameters: 172996
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

172997
type: LocalParameter
units: 491513
value: 1.5084E-13

172996
type: LocalParameter
units: 491549
value: 1.18513155294E-12

493149
type: SpeciesReference
stoichiometry: 1.0
species: 562353

493136
type: SpeciesReference
stoichiometry: 1.0
species: 562313

493124
type: SpeciesReference
stoichiometry: 1.0
species: 562293

491610
type: SBMLUnit
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE

563632
type: Reaction
kinetic law: 493306
product: 493294
product: 493282
reactant: 493270
fast: false
reversible: false

493306
type: KineticLaw
local parameters: 173002
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

173002
type: LocalParameter
units: 491513
value: 3.771E-14

493294
type: SpeciesReference
stoichiometry: 1.0
species: 562373

493282
type: SpeciesReference
stoichiometry: 1.0
species: 562293

493270
type: SpeciesReference
stoichiometry: 1.0
species: 562393

563872
type: Reaction
kinetic law: 493887
product: 493874
product: 493862
reactant: 493850
fast: false
reversible: false

173022
type: LocalParameter
units: 491513
value: 7.542E-13

493874
type: SpeciesReference
stoichiometry: 1.0
species: 562472

493862
type: SpeciesReference
stoichiometry: 1.0
species: 562153

493850
type: SpeciesReference
stoichiometry: 1.0
species: 562512

563792
type: Reaction
kinetic law: 493694
product: 493682
product: 493670
reactant: 493658
fast: false
reversible: false

173015
type: LocalParameter
units: 491513
value: 7.542E-13

493682
type: SpeciesReference
stoichiometry: 1.0
species: 562472

493670
type: SpeciesReference
stoichiometry: 1.0
species: 562113

493658
type: SpeciesReference
stoichiometry: 1.0
species: 562473

563732
type: Reaction
kinetic law: 493548
product: 493536
reactant: 493524
reactant: 493512
notes: See MKP1-tyr-deph
fast: false
reversible: true

493548
type: KineticLaw
local parameters: 173011
local parameters: 173010
notes: k1*MAPK_star_*MKP_minus_1-k2*MKP_minus_1_slash_MKP1_minus_thr_minus_deph_slash_MKP1_minus_thr_minus_deph_cplx

173011
type: LocalParameter
units: 491513
value: 2.0112E-12

173010
type: LocalParameter
units: 491549
value: 3.59141977602E-13

493536
type: SpeciesReference
stoichiometry: 1.0
species: 562453

493524
type: SpeciesReference
stoichiometry: 1.0
species: 562433

562433
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.02
initial amount: NaN
in compartment: 561853

493512
type: SpeciesReference
stoichiometry: 1.0
species: 562073

563972
type: Reaction
kinetic law: 494129
product: 494117
reactant: 494105
reactant: 494093
notes: Kinetics same as GEF-bg-act-ras
fast: false
reversible: true

494129
type: KineticLaw
local parameters: 173030
local parameters: 173029
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

173030
type: LocalParameter
units: 491513
value: 1.0056E-14

173029
type: LocalParameter
units: 491549
value: 2.48886158382E-14

494117
type: SpeciesReference
stoichiometry: 1.0
species: 562572

494105
type: SpeciesReference
stoichiometry: 1.0
species: 562553

494093
type: SpeciesReference
stoichiometry: 1.0
species: 562592

562592
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 561853

563192
type: Reaction
kinetic law: 492275
product: 492263
reactant: 492251
reactant: 492239
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

492275
type: KineticLaw
local parameters: 172960
local parameters: 172958
notes: kf*MAPK_slash_craf_minus_1*Ras_slash_GTP_minus_Ras-kb*MAPK_slash_Raf_minus_GTP_minus_Ras

172960
type: LocalParameter
units: 491513
value: 0.0

172958
type: LocalParameter
units: 491549
value: 0.0

492263
type: SpeciesReference
stoichiometry: 1.0
species: 562313

492251
type: SpeciesReference
stoichiometry: 1.0
species: 562573

492239
type: SpeciesReference
stoichiometry: 1.0
species: 562113

563013
type: Reaction
kinetic law: 491780
product: 491768
reactant: 491755
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

491780
type: KineticLaw
local parameters: 172927
local parameters: 172925
notes: kf*PKC_slash_PKC_minus_Ca_minus_DAG-kb*PKC_slash_PKC_minus_DAG_minus_memb_star_

172927
type: LocalParameter
units: 491513
value: 1.257E-14

172925
type: LocalParameter
units: 491513
value: 1.257E-13

491768
type: SpeciesReference
stoichiometry: 1.0
species: 561913

491755
type: SpeciesReference
stoichiometry: 1.0
species: 561933

563292
type: Reaction
kinetic law: 492480
product: 492468
reactant: 492456
reactant: 492444
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

492480
type: KineticLaw
local parameters: 172974
local parameters: 172973
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

172974
type: LocalParameter
units: 491513
value: 2.0112E-12

172973
type: LocalParameter
units: 491549
value: 1.25699218146E-13

492468
type: SpeciesReference
stoichiometry: 1.0
species: 562013

492456
type: SpeciesReference
stoichiometry: 1.0
species: 562932

492444
type: SpeciesReference
stoichiometry: 1.0
species: 562113

562452
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853

563072
type: Reaction
kinetic law: 491950
product: 491938
reactant: 491926
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

491950
type: KineticLaw
local parameters: 172939
local parameters: 172937
notes: kf*Ras_slash_GTP_minus_Ras-kb*Ras_slash_GDP_minus_Ras

172939
type: LocalParameter
units: 491513
value: 0.0

172937
type: LocalParameter
units: 491513
value: 1.257E-17

491938
type: SpeciesReference
stoichiometry: 1.0
species: 562592

491926
type: SpeciesReference
stoichiometry: 1.0
species: 562573

563172
type: Reaction
kinetic law: 492227
product: 492215
reactant: 492203
reactant: 492191
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 !) 19 May 2006. Splitting the old CaM-TR2-bind-Ca reaction into two steps, each binding 1 Ca. This improves numerical stability and is conceptually better too. Overall rates are the same, so each kf and kb is the square root of the earlier ones. So kf = 1.125e-4, kb = 8.4853
fast: false
reversible: true

492227
type: KineticLaw
local parameters: 172957
local parameters: 172955
notes: kf*CaM_slash_CaM_minus_Ca*Ca-kb*CaM_slash_CaM_minus_Ca2

172957
type: LocalParameter
units: 491513
value: 1.06660221E-12

172955
type: LocalParameter
units: 491549
value: 1.066533075E-12

492215
type: SpeciesReference
stoichiometry: 1.0
species: 562692

492203
type: SpeciesReference
stoichiometry: 1.0
species: 562732

492191
type: SpeciesReference
stoichiometry: 1.0
species: 562712

563392
type: Reaction
kinetic law: 492723
product: 492711
product: 492699
reactant: 492687
fast: false
reversible: false

492723
type: KineticLaw
local parameters: 172983
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_GEF_slash_PKC_minus_act_minus_GEF_cplx

172983
type: LocalParameter
units: 491513
value: 5.028E-13

492711
type: SpeciesReference
stoichiometry: 1.0
species: 562932

492699
type: SpeciesReference
stoichiometry: 1.0
species: 562553

492687
type: SpeciesReference
stoichiometry: 1.0
species: 562053

562533
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853

563532
type: Reaction
kinetic law: 493064
product: 493052
reactant: 493040
reactant: 493028
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

493064
type: KineticLaw
local parameters: 172994
local parameters: 172993
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

172994
type: LocalParameter
units: 491513
value: 1.5084E-13

172993
type: LocalParameter
units: 491549
value: 1.18513155294E-12

493052
type: SpeciesReference
stoichiometry: 1.0
species: 562333

493040
type: SpeciesReference
stoichiometry: 1.0
species: 562313

493028
type: SpeciesReference
stoichiometry: 1.0
species: 562153

563752
type: Reaction
kinetic law: 493598
product: 493585
product: 493572
reactant: 493560
fast: false
reversible: false

493598
type: KineticLaw
local parameters: 173012
notes: k3*MKP_minus_1_slash_MKP1_minus_thr_minus_deph_slash_MKP1_minus_thr_minus_deph_cplx

173012
type: LocalParameter
units: 491513
value: 5.028E-13

493585
type: SpeciesReference
stoichiometry: 1.0
species: 562433

493572
type: SpeciesReference
stoichiometry: 1.0
species: 562213

562213
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853

493560
type: SpeciesReference
stoichiometry: 1.0
species: 562453

563033
type: Reaction
kinetic law: 491829
product: 491817
reactant: 491805
reactant: 491793
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

491829
type: KineticLaw
local parameters: 172930
local parameters: 172928
notes: kf*PKC_slash_PKC_minus_cytosolic*DAG-kb*PKC_slash_PKC_minus_DAG

172930
type: LocalParameter
units: 491513
value: 1.257E-14

172928
type: LocalParameter
units: 491549
value: 7.5420478917E-17

491817
type: SpeciesReference
stoichiometry: 1.0
species: 561953

561953
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.16100503845134E-16
initial amount: NaN
in compartment: 561853

491805
type: SpeciesReference
stoichiometry: 1.0
species: 562852

491793
type: SpeciesReference
stoichiometry: 1.0
species: 561973

564032
type: Reaction
kinetic law: 494273
product: 494261
product: 494249
reactant: 494237
fast: false
reversible: false

494273
type: KineticLaw
local parameters: 173035
notes: k3*Ras_slash_GAP_slash_GAP_minus_inact_minus_ras_slash_GAP_minus_inact_minus_ras_cplx

173035
type: LocalParameter
units: 491513
value: 1.257E-12

494261
type: SpeciesReference
stoichiometry: 1.0
species: 562612

494249
type: SpeciesReference
stoichiometry: 1.0
species: 562592

494237
type: SpeciesReference
stoichiometry: 1.0
species: 562613

562652
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 20.0
initial amount: NaN
in compartment: 561853

563012
type: Reaction
kinetic law: 491743
product: 491731
reactant: 491719
fast: false
reversible: true

491743
type: KineticLaw
local parameters: 172924
local parameters: 172922
notes: kf*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_memb_star_

172924
type: LocalParameter
units: 491513
value: 4.4027682E-13

172922
type: LocalParameter
units: 491513
value: 1.5970185E-13

491731
type: SpeciesReference
stoichiometry: 1.0
species: 561893

491719
type: SpeciesReference
stoichiometry: 1.0
species: 561873

564052
type: Reaction
kinetic law: 494321
product: 494309
reactant: 494297
reactant: 494285
notes: Kinetics same as GEF-bg_act-ras, but as of March 17, 2006, the kcat is scaled from 0.02 to 0.2 to have a stronger Ca response for the direct MAPK input.
fast: false
reversible: true

494321
type: KineticLaw
local parameters: 173037
local parameters: 173036
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

173037
type: LocalParameter
units: 491513
value: 1.0056E-13

173036
type: LocalParameter
units: 491549
value: 2.48886158382E-13

494309
type: SpeciesReference
stoichiometry: 1.0
species: 562633

494297
type: SpeciesReference
stoichiometry: 1.0
species: 562632

494285
type: SpeciesReference
stoichiometry: 1.0
species: 562592

563232
type: Reaction
kinetic law: 492348
product: 492336
reactant: 492323
fast: false
reversible: true

492348
type: KineticLaw
local parameters: 172965
local parameters: 172964
notes: kf*PKM_slash_PKM_synthesis-kb*PKM_slash_PKM_activator

172965
type: LocalParameter
units: 491513
value: 0.0

172964
type: LocalParameter
units: 491513
value: 1.257E-16

492336
type: SpeciesReference
stoichiometry: 1.0
species: 562832

492323
type: SpeciesReference
stoichiometry: 1.0
species: 562772

563472
type: Reaction
kinetic law: 492918
product: 492906
product: 492894
reactant: 492882
fast: false
reversible: false

492918
type: KineticLaw
local parameters: 172989
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx

172989
type: LocalParameter
units: 491513
value: 3.771E-14

492906
type: SpeciesReference
stoichiometry: 1.0
species: 562233

492894
type: SpeciesReference
stoichiometry: 1.0
species: 562213

492882
type: SpeciesReference
stoichiometry: 1.0
species: 562253

563092
type: Reaction
kinetic law: 491986
product: 491974
reactant: 491962
notes: Assume a reasonably good rate for dephosphorylating it, 1/sec
fast: false
reversible: true

491986
type: KineticLaw
local parameters: 172942
local parameters: 172940
notes: kf*Ras_slash_GAP_star_-kb*Ras_slash_GAP

172942
type: LocalParameter
units: 491513
value: 0.0

172940
type: LocalParameter
units: 491513
value: 1.257E-14

491974
type: SpeciesReference
stoichiometry: 1.0
species: 562612

491962
type: SpeciesReference
stoichiometry: 1.0
species: 562593

563692
type: Reaction
kinetic law: 493452
product: 493440
reactant: 493428
reactant: 493416
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

493452
type: KineticLaw
local parameters: 173008
local parameters: 173007
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

173008
type: LocalParameter
units: 491513
value: 2.0112E-12

173007
type: LocalParameter
units: 491549
value: 3.59141977602E-13

493440
type: SpeciesReference
stoichiometry: 1.0
species: 562452

493428
type: SpeciesReference
stoichiometry: 1.0
species: 562433

493416
type: SpeciesReference
stoichiometry: 1.0
species: 562213

563113
type: Reaction
kinetic law: 492082
product: 492070
reactant: 492058
reactant: 492046
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

492082
type: KineticLaw
local parameters: 172948
local parameters: 172946
notes: kf*CaM_slash_CaM_minus_Ca3*Ca-kb*CaM_slash_CaM_minus_Ca4

172948
type: LocalParameter
units: 491513
value: 1.257E-12

172946
type: LocalParameter
units: 491549
value: 5.8450752657E-14

492070
type: SpeciesReference
stoichiometry: 1.0
species: 562673

492058
type: SpeciesReference
stoichiometry: 1.0
species: 562732

492046
type: SpeciesReference
stoichiometry: 1.0
species: 562672

563812
type: Reaction
kinetic law: 493742
product: 493730
reactant: 493718
reactant: 493706
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

173017
type: LocalParameter
units: 491513
value: 3.0168E-12

173016
type: LocalParameter
units: 491549
value: 2.40856349364E-13

493730
type: SpeciesReference
stoichiometry: 1.0
species: 562493

493718
type: SpeciesReference
stoichiometry: 1.0
species: 562472

493706
type: SpeciesReference
stoichiometry: 1.0
species: 562233

563992
type: Reaction
kinetic law: 494177
product: 494165
product: 494153
reactant: 494141
fast: false
reversible: false

494177
type: KineticLaw
local parameters: 173031
notes: k3*Ras_slash_GEF_star__slash_GEF_star__minus_act_minus_ras_slash_GEF_star__minus_act_minus_ras_cplx

173031
type: LocalParameter
units: 491513
value: 2.514E-15

494165
type: SpeciesReference
stoichiometry: 1.0
species: 562553

494153
type: SpeciesReference
stoichiometry: 1.0
species: 562573

494141
type: SpeciesReference
stoichiometry: 1.0
species: 562572

563932
type: Reaction
kinetic law: 494032
product: 494019
reactant: 494007
reactant: 493995
fast: false
reversible: true

494032
type: KineticLaw
local parameters: 173027
local parameters: 173026
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

173027
type: LocalParameter
units: 491513
value: 1.0056E-14

173026
type: LocalParameter
units: 491549
value: 1.24438339044E-15

494019
type: SpeciesReference
stoichiometry: 1.0
species: 562533

494007
type: SpeciesReference
stoichiometry: 1.0
species: 562532

493995
type: SpeciesReference
stoichiometry: 1.0
species: 562592

564132
type: Reaction
kinetic law: 494515
product: 494503
reactant: 494491
reactant: 494479
fast: false
reversible: true

494515
type: KineticLaw
local parameters: 173044
local parameters: 173042
notes: k1*PKM_slash_PKM_activator*PKM_slash_Ca_dot_detector_complex-k2*PKM_slash_Ca_dot_detector_complex_slash_kenz_slash_kenz_cplx

173044
type: LocalParameter
units: 491513
value: 1.0056E-13

173042
type: LocalParameter
units: 491549
value: 2.51398436292E-14

494503
type: SpeciesReference
stoichiometry: 1.0
species: 562812

494491
type: SpeciesReference
stoichiometry: 1.0
species: 562793

494479
type: SpeciesReference
stoichiometry: 1.0
species: 562832

563252
type: Reaction
kinetic law: 492396
product: 492384
reactant: 492372
reactant: 492360
fast: false
reversible: true

492396
type: KineticLaw
local parameters: 172968
local parameters: 172967
notes: kf*PKM_slash_Ca_detector*CaM_slash_CaM_minus_Ca4-kb*PKM_slash_Ca_dot_detector_complex

172968
type: LocalParameter
units: 491513
value: 1.257E-13

172967
type: LocalParameter
units: 491549
value: 1.25699218146E-12

492384
type: SpeciesReference
stoichiometry: 1.0
species: 562793

492372
type: SpeciesReference
stoichiometry: 1.0
species: 562673

492360
type: SpeciesReference
stoichiometry: 1.0
species: 562752

563492
type: Reaction
kinetic law: 492967
product: 492955
reactant: 492943
reactant: 492930
notes: Rate consts same as for MAPKKtyr.
fast: false
reversible: true

492967
type: KineticLaw
local parameters: 172991
local parameters: 172990
notes: k1*MAPK_slash_MAPK_minus_tyr*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx

172991
type: LocalParameter
units: 491513
value: 1.5084E-13

172990
type: LocalParameter
units: 491549
value: 4.07263949946E-12

492955
type: SpeciesReference
stoichiometry: 1.0
species: 562273

492943
type: SpeciesReference
stoichiometry: 1.0
species: 562233

492930
type: SpeciesReference
stoichiometry: 1.0
species: 562213

563132
type: Reaction
kinetic law: 492131
product: 492119
reactant: 492107
reactant: 492094
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 !) 19 May 2006. Splitting the old CaM-TR2-bind-Ca reaction into two steps, each binding 1 Ca. This improves numerical stability and is conceptually better too. Overall rates are the same, so each kf and kb is the square root of the earlier ones. So kf = 1.125e-4, kb = 8.4853
fast: false
reversible: true

492131
type: KineticLaw
local parameters: 172951
local parameters: 172949
notes: kf*CaM_slash_CaM*Ca-kb*CaM_slash_CaM_minus_Ca

172951
type: LocalParameter
units: 491513
value: 1.06660221E-12

172949
type: LocalParameter
units: 491549
value: 1.066533075E-12

492119
type: SpeciesReference
stoichiometry: 1.0
species: 562712

492107
type: SpeciesReference
stoichiometry: 1.0
species: 562732

492094
type: SpeciesReference
stoichiometry: 1.0
species: 562652

563432
type: Reaction
kinetic law: 492820
product: 492808
product: 492796
reactant: 492784
fast: false
reversible: false

492820
type: KineticLaw
local parameters: 172986
notes: k3*MAPK_star__slash_MAPK_star__minus_feedback_slash_MAPK_star__minus_feedback_cplx

172986
type: LocalParameter
units: 491513
value: 1.257E-12

492808
type: SpeciesReference
stoichiometry: 1.0
species: 562073

492796
type: SpeciesReference
stoichiometry: 1.0
species: 562193

492784
type: SpeciesReference
stoichiometry: 1.0
species: 562093

563352
type: Reaction
kinetic law: 492625
product: 492613
product: 492601
reactant: 492589
fast: false
reversible: false

492625
type: KineticLaw
local parameters: 172980
notes: k3*PKC_minus_active_slash_PKC_minus_inact_minus_GAP_slash_PKC_minus_inact_minus_GAP_cplx

172980
type: LocalParameter
units: 491513
value: 5.028E-13

492613
type: SpeciesReference
stoichiometry: 1.0
species: 562932

492601
type: SpeciesReference
stoichiometry: 1.0
species: 562593

492589
type: SpeciesReference
stoichiometry: 1.0
species: 562033

563592
type: Reaction
kinetic law: 493210
product: 493197
product: 493185
reactant: 493173
fast: false
reversible: false

493210
type: KineticLaw
local parameters: 172998
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

172998
type: LocalParameter
units: 491513
value: 3.771E-14

493197
type: SpeciesReference
stoichiometry: 1.0
species: 562313

493185
type: SpeciesReference
stoichiometry: 1.0
species: 562233

493173
type: SpeciesReference
stoichiometry: 1.0
species: 562353

563832
type: Reaction
kinetic law: 493790
product: 493778
product: 493766
reactant: 493754
fast: false
reversible: false

173018
type: LocalParameter
units: 491513
value: 7.542E-13

493778
type: SpeciesReference
stoichiometry: 1.0
species: 562472

493766
type: SpeciesReference
stoichiometry: 1.0
species: 562293

493754
type: SpeciesReference
stoichiometry: 1.0
species: 562493

563652
type: Reaction
kinetic law: 493355
product: 493343
reactant: 493331
reactant: 493318
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

493355
type: KineticLaw
local parameters: 173005
local parameters: 173003
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

173005
type: LocalParameter
units: 491513
value: 1.5084E-13

173003
type: LocalParameter
units: 491549
value: 1.18513155294E-12

493343
type: SpeciesReference
stoichiometry: 1.0
species: 562413

493331
type: SpeciesReference
stoichiometry: 1.0
species: 562373

493318
type: SpeciesReference
stoichiometry: 1.0
species: 562293

563712
type: Reaction
kinetic law: 493500
product: 493488
product: 493476
reactant: 493464
fast: false
reversible: false

493500
type: KineticLaw
local parameters: 173009
notes: k3*MKP_minus_1_slash_MKP1_minus_tyr_minus_deph_slash_MKP1_minus_tyr_minus_deph_cplx

173009
type: LocalParameter
units: 491513
value: 5.028E-13

493488
type: SpeciesReference
stoichiometry: 1.0
species: 562433

493476
type: SpeciesReference
stoichiometry: 1.0
species: 562173

493464
type: SpeciesReference
stoichiometry: 1.0
species: 562452

563952
type: Reaction
kinetic law: 494080
product: 494068
product: 494056
reactant: 494044
fast: false
reversible: false

494080
type: KineticLaw
local parameters: 173028
notes: k3*Ras_slash_inact_minus_GEF_slash_basal_GEF_activity_slash_basal_GEF_activity_cplx

173028
type: LocalParameter
units: 491513
value: 2.514E-15

494068
type: SpeciesReference
stoichiometry: 1.0
species: 562532

494056
type: SpeciesReference
stoichiometry: 1.0
species: 562573

494044
type: SpeciesReference
stoichiometry: 1.0
species: 562533