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

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

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

493052
stoichiometry: 1.0
species: 562333
type: SpeciesReference

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

493766
stoichiometry: 1.0
species: 562293
type: SpeciesReference

494237
stoichiometry: 1.0
species: 562613
type: SpeciesReference

492748
stoichiometry: 1.0
species: 562073
type: SpeciesReference

494333
stoichiometry: 1.0
species: 562633
type: SpeciesReference

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

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

494393
stoichiometry: 1.0
species: 562772
type: SpeciesReference

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

493428
stoichiometry: 1.0
species: 562433
type: SpeciesReference

492360
stoichiometry: 1.0
species: 562752
type: SpeciesReference

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

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

563192
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
type: Reaction

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

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

492796
stoichiometry: 1.0
species: 562193
type: SpeciesReference

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

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

493368
stoichiometry: 1.0
species: 562413
type: SpeciesReference

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

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

492263
stoichiometry: 1.0
species: 562313
type: SpeciesReference

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

493778
stoichiometry: 1.0
species: 562472
type: SpeciesReference

562872
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
type: Species

493706
stoichiometry: 1.0
species: 562233
type: SpeciesReference

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

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

493355
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
type: KineticLaw

493064
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
type: KineticLaw

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

493004
stoichiometry: 1.0
species: 562233
type: SpeciesReference

494381
stoichiometry: 1.0
species: 562872
type: SpeciesReference

493754
stoichiometry: 1.0
species: 562493
type: SpeciesReference

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

492107
stoichiometry: 1.0
species: 562732
type: SpeciesReference

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

494345
stoichiometry: 1.0
species: 562573
type: SpeciesReference

494225
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
type: KineticLaw

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

563452
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
type: Reaction

491974
stoichiometry: 1.0
species: 562612
type: SpeciesReference

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

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

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

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

492336
stoichiometry: 1.0
species: 562832
type: SpeciesReference

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

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

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

494430
stoichiometry: 1.0
species: 562792
type: SpeciesReference

492735
stoichiometry: 1.0
species: 562133
type: SpeciesReference

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

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

492275
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
type: KineticLaw

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

492119
stoichiometry: 1.0
species: 562712
type: SpeciesReference

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

494044
stoichiometry: 1.0
species: 562533
type: SpeciesReference

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

494093
stoichiometry: 1.0
species: 562592
type: SpeciesReference

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

492384
stoichiometry: 1.0
species: 562793
type: SpeciesReference

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

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

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

493343
stoichiometry: 1.0
species: 562413
type: SpeciesReference

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

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

561853
constant: true
size: 1.5E-15
spatial dimensions: 3.0
type: Compartment

492323
stoichiometry: 1.0
species: 562772
type: SpeciesReference

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

492287
stoichiometry: 1.0
species: 561993
type: SpeciesReference

491695
stoichiometry: 1.0
species: 561933
type: SpeciesReference

562113
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 561853
type: Species

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

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

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

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

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

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

491962
stoichiometry: 1.0
species: 562593
type: SpeciesReference

493802
stoichiometry: 1.0
species: 562293
type: SpeciesReference

562013
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853
type: Species

491622
stoichiometry: 1.0
species: 561973
type: SpeciesReference

492070
stoichiometry: 1.0
species: 562673
type: SpeciesReference

562093
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853
type: Species

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

493730
stoichiometry: 1.0
species: 562493
type: SpeciesReference

494189
stoichiometry: 1.0
species: 562573
type: SpeciesReference

494321
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
type: KineticLaw

494249
stoichiometry: 1.0
species: 562592
type: SpeciesReference

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

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

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

493682
stoichiometry: 1.0
species: 562472
type: SpeciesReference

493331
stoichiometry: 1.0
species: 562373
type: SpeciesReference

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

494032
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
type: KineticLaw

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

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

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

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

491635
stoichiometry: 1.0
species: 562732
type: SpeciesReference

493040
stoichiometry: 1.0
species: 562313
type: SpeciesReference

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

492372
stoichiometry: 1.0
species: 562673
type: SpeciesReference

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

172982
units: 491513
value: 2.0112E-12
type: LocalParameter

563132
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
type: Reaction

562792
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853
type: Species

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

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

563033
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
type: Reaction

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

493718
stoichiometry: 1.0
species: 562472
type: SpeciesReference

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

563172
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
type: Reaction

492711
stoichiometry: 1.0
species: 562932
type: SpeciesReference

491683
stoichiometry: 1.0
species: 561873
type: SpeciesReference

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

492299
stoichiometry: 1.0
species: 562892
type: SpeciesReference

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

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

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

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

562053
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853
type: Species

562732
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.08
initial amount: NaN
in compartment: 561853
type: Species

493814
stoichiometry: 1.0
species: 562472
type: SpeciesReference

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

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

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

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

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

492650
stoichiometry: 1.0
species: 562932
type: SpeciesReference

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

563572
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
type: Reaction

492167
stoichiometry: 1.0
species: 562672
type: SpeciesReference

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

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

562892
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853
type: Species

564112
kinetic law: 494466
product: 494454
product: 494442
reactant: 494430
fast: false
reversible: false
type: Reaction

492601
stoichiometry: 1.0
species: 562593
type: SpeciesReference

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

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

493585
stoichiometry: 1.0
species: 562433
type: SpeciesReference

491853
stoichiometry: 1.0
species: 562573
type: SpeciesReference

492663
stoichiometry: 1.0
species: 562053
type: SpeciesReference

493911
stoichiometry: 1.0
species: 562472
type: SpeciesReference

491731
stoichiometry: 1.0
species: 561893
type: SpeciesReference

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

562273
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853
type: Species

491647
stoichiometry: 1.0
species: 561873
type: SpeciesReference

493572
stoichiometry: 1.0
species: 562213
type: SpeciesReference

494539
stoichiometry: 1.0
species: 562772
type: SpeciesReference

492492
stoichiometry: 1.0
species: 562013
type: SpeciesReference

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

493670
stoichiometry: 1.0
species: 562113
type: SpeciesReference

493306
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
type: KineticLaw

493622
stoichiometry: 1.0
species: 562472
type: SpeciesReference

492468
stoichiometry: 1.0
species: 562013
type: SpeciesReference

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

492760
stoichiometry: 1.0
species: 562093
type: SpeciesReference

492155
stoichiometry: 1.0
species: 562732
type: SpeciesReference

492516
stoichiometry: 1.0
species: 562932
type: SpeciesReference

493488
stoichiometry: 1.0
species: 562433
type: SpeciesReference

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

492808
stoichiometry: 1.0
species: 562073
type: SpeciesReference

492613
stoichiometry: 1.0
species: 562932
type: SpeciesReference

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

491841
stoichiometry: 1.0
species: 562133
type: SpeciesReference

492675
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
type: KineticLaw

493923
stoichiometry: 1.0
species: 562513
type: SpeciesReference

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

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

494479
stoichiometry: 1.0
species: 562832
type: SpeciesReference

562993
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
type: Reaction

494105
stoichiometry: 1.0
species: 562553
type: SpeciesReference

492480
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
type: KineticLaw

493634
stoichiometry: 1.0
species: 562473
type: SpeciesReference

563692
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
type: Reaction

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

562133
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853
type: Species

492894
stoichiometry: 1.0
species: 562213
type: SpeciesReference

563612
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
type: Reaction

563052
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
type: Reaction

494442
stoichiometry: 1.0
species: 561993
type: SpeciesReference

493282
stoichiometry: 1.0
species: 562293
type: SpeciesReference

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

492408
stoichiometry: 1.0
species: 562912
type: SpeciesReference

493476
stoichiometry: 1.0
species: 562173
type: SpeciesReference

492456
stoichiometry: 1.0
species: 562932
type: SpeciesReference

492504
stoichiometry: 1.0
species: 562133
type: SpeciesReference

492772
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
type: KineticLaw

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

492143
stoichiometry: 1.0
species: 562692
type: SpeciesReference

493076
stoichiometry: 1.0
species: 562333
type: SpeciesReference

172960
units: 491513
value: 0.0
type: LocalParameter

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

494117
stoichiometry: 1.0
species: 562572
type: SpeciesReference

562692
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853
type: Species

493404
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
type: KineticLaw

492687
stoichiometry: 1.0
species: 562053
type: SpeciesReference

563652
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
type: Reaction

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

491755
stoichiometry: 1.0
species: 561933
type: SpeciesReference

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

562672
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853
type: Species

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

494454
stoichiometry: 1.0
species: 562772
type: SpeciesReference

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

562932
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853
type: Species

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

492882
stoichiometry: 1.0
species: 562253
type: SpeciesReference

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

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

491793
stoichiometry: 1.0
species: 561973
type: SpeciesReference

494405
stoichiometry: 1.0
species: 562792
type: SpeciesReference

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

492784
stoichiometry: 1.0
species: 562093
type: SpeciesReference

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

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

563013
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
type: Reaction

493270
stoichiometry: 1.0
species: 562393
type: SpeciesReference

493464
stoichiometry: 1.0
species: 562452
type: SpeciesReference

491719
stoichiometry: 1.0
species: 561873
type: SpeciesReference

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

491768
stoichiometry: 1.0
species: 561913
type: SpeciesReference

492444
stoichiometry: 1.0
species: 562113
type: SpeciesReference

563152
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
type: Reaction

493318
stoichiometry: 1.0
species: 562293
type: SpeciesReference

493610
stoichiometry: 1.0
species: 562133
type: SpeciesReference

494129
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
type: KineticLaw

493416
stoichiometry: 1.0
species: 562213
type: SpeciesReference

493560
stoichiometry: 1.0
species: 562453
type: SpeciesReference

493088
stoichiometry: 1.0
species: 562293
type: SpeciesReference

494491
stoichiometry: 1.0
species: 562793
type: SpeciesReference

172962
units: 491513
value: 0.0
type: LocalParameter

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

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

492699
stoichiometry: 1.0
species: 562553
type: SpeciesReference

493947
stoichiometry: 1.0
species: 562513
type: SpeciesReference

562073
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853
type: Species

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

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

493850
stoichiometry: 1.0
species: 562512
type: SpeciesReference

492832
stoichiometry: 1.0
species: 562173
type: SpeciesReference

172952
units: 491549
value: 4.52522873502E-13
type: LocalParameter

492540
stoichiometry: 1.0
species: 562612
type: SpeciesReference

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

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

494503
stoichiometry: 1.0
species: 562812
type: SpeciesReference

491865
stoichiometry: 1.0
species: 562373
type: SpeciesReference

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

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

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

493440
stoichiometry: 1.0
species: 562452
type: SpeciesReference

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

493512
stoichiometry: 1.0
species: 562073
type: SpeciesReference

562812
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853
type: Species

562972
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
type: Reaction

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

492979
stoichiometry: 1.0
species: 562273
type: SpeciesReference

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

492022
stoichiometry: 1.0
species: 562632
type: SpeciesReference

493392
stoichiometry: 1.0
species: 562373
type: SpeciesReference

172965
units: 491513
value: 0.0
type: LocalParameter

494418
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
type: KineticLaw

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

493959
stoichiometry: 1.0
species: 562133
type: SpeciesReference

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

491901
stoichiometry: 1.0
species: 562532
type: SpeciesReference

563892
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
type: Reaction

494297
stoichiometry: 1.0
species: 562632
type: SpeciesReference

491877
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
type: KineticLaw

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

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

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

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

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

493452
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
type: KineticLaw

491561
exponent: 2.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

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

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

493524
stoichiometry: 1.0
species: 562433
type: SpeciesReference

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

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

493380
stoichiometry: 1.0
species: 562233
type: SpeciesReference

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

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

491817
stoichiometry: 1.0
species: 561953
type: SpeciesReference

493100
stoichiometry: 1.0
species: 562313
type: SpeciesReference

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

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

564012
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
type: Reaction

492564
stoichiometry: 1.0
species: 562033
type: SpeciesReference

494527
stoichiometry: 1.0
species: 562812
type: SpeciesReference

563412
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
type: Reaction

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

492239
stoichiometry: 1.0
species: 562113
type: SpeciesReference

491889
stoichiometry: 1.0
species: 562553
type: SpeciesReference

491938
stoichiometry: 1.0
species: 562592
type: SpeciesReference

172942
units: 491513
value: 0.0
type: LocalParameter

562353
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853
type: Species

494285
stoichiometry: 1.0
species: 562592
type: SpeciesReference

562453
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853
type: Species

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

564092
kinetic law: 494418
product: 494405
reactant: 494393
reactant: 494381
fast: false
reversible: true
type: Reaction

492589
stoichiometry: 1.0
species: 562033
type: SpeciesReference

493258
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
type: KineticLaw

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

562772
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.001
initial amount: NaN
in compartment: 561853
type: Species

493294
stoichiometry: 1.0
species: 562373
type: SpeciesReference

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

564052
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
type: Reaction

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

493536
stoichiometry: 1.0
species: 562453
type: SpeciesReference

563372
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
type: Reaction

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

491573
exponent: -1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

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

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

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

494515
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
type: KineticLaw

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

491926
stoichiometry: 1.0
species: 562573
type: SpeciesReference

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

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

492638
stoichiometry: 1.0
species: 562532
type: SpeciesReference

492552
stoichiometry: 1.0
species: 562932
type: SpeciesReference

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

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

172958
units: 491549
value: 0.0
type: LocalParameter

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

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

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

492010
stoichiometry: 1.0
species: 562673
type: SpeciesReference

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

492577
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
type: KineticLaw

563332
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
type: Reaction

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

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

493246
stoichiometry: 1.0
species: 562393
type: SpeciesReference

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

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

493995
stoichiometry: 1.0
species: 562592
type: SpeciesReference

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

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

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

493548
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
type: KineticLaw

493658
stoichiometry: 1.0
species: 562473
type: SpeciesReference

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

494551
stoichiometry: 1.0
species: 562793
type: SpeciesReference

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

492906
stoichiometry: 1.0
species: 562233
type: SpeciesReference

493899
stoichiometry: 1.0
species: 562193
type: SpeciesReference

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

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

493136
stoichiometry: 1.0
species: 562313
type: SpeciesReference

491998
stoichiometry: 1.0
species: 562532
type: SpeciesReference

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

493234
stoichiometry: 1.0
species: 562373
type: SpeciesReference

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

492191
stoichiometry: 1.0
species: 562712
type: SpeciesReference

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

562233
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853
type: Species

494261
stoichiometry: 1.0
species: 562612
type: SpeciesReference

562253
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853
type: Species

561993
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.01
initial amount: NaN
in compartment: 561853
type: Species

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

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

494201
stoichiometry: 1.0
species: 562612
type: SpeciesReference

494369
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
type: KineticLaw

493185
stoichiometry: 1.0
species: 562233
type: SpeciesReference

492991
stoichiometry: 1.0
species: 562073
type: SpeciesReference

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

493028
stoichiometry: 1.0
species: 562153
type: SpeciesReference

494165
stoichiometry: 1.0
species: 562553
type: SpeciesReference

492215
stoichiometry: 1.0
species: 562692
type: SpeciesReference

493149
stoichiometry: 1.0
species: 562353
type: SpeciesReference

494056
stoichiometry: 1.0
species: 562573
type: SpeciesReference

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

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

492869
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
type: KineticLaw

493971
stoichiometry: 1.0
species: 562472
type: SpeciesReference

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

493826
stoichiometry: 1.0
species: 562512
type: SpeciesReference

491671
stoichiometry: 1.0
species: 562852
type: SpeciesReference

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

493222
stoichiometry: 1.0
species: 562153
type: SpeciesReference

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

492943
stoichiometry: 1.0
species: 562233
type: SpeciesReference

MODEL9147232940
species: 562353
reaction: 563212
species: 562253
volume units: 679943
species: 562812
reaction: 563152
reaction: 564072
species: 562593
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
area units: area
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
species: 562532
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
reaction: 563112
species: 561893
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
species: 562452
reaction: 563072

494213
stoichiometry: 1.0
species: 562613
type: SpeciesReference

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

493197
stoichiometry: 1.0
species: 562313
type: SpeciesReference

494357
stoichiometry: 1.0
species: 562632
type: SpeciesReference

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

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

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

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

494068
stoichiometry: 1.0
species: 562532
type: SpeciesReference

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

563072
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
type: Reaction

492203
stoichiometry: 1.0
species: 562732
type: SpeciesReference

493210
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
type: KineticLaw

494007
stoichiometry: 1.0
species: 562532
type: SpeciesReference

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

492955
stoichiometry: 1.0
species: 562273
type: SpeciesReference

491805
stoichiometry: 1.0
species: 562852
type: SpeciesReference

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

493112
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
type: KineticLaw

492251
stoichiometry: 1.0
species: 562573
type: SpeciesReference

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

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

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

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

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

492046
stoichiometry: 1.0
species: 562672
type: SpeciesReference

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

172936
units: 491513
value: 0.0
type: LocalParameter

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

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

562553
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853
type: Species

172976
units: 491513
value: 5.028E-13
type: LocalParameter

492420
stoichiometry: 1.0
species: 562732
type: SpeciesReference

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

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

493161
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
type: KineticLaw

562532
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.1
initial amount: NaN
in compartment: 561853
type: Species

562573
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853
type: Species

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

494141
stoichiometry: 1.0
species: 562572
type: SpeciesReference

493874
stoichiometry: 1.0
species: 562472
type: SpeciesReference

492856
stoichiometry: 1.0
species: 562253
type: SpeciesReference

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

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

563312
kinetic law: 492528
product: 492516
product: 492504
reactant: 492492
fast: false
reversible: false
type: Reaction

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

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

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

494019
stoichiometry: 1.0
species: 562533
type: SpeciesReference

492058
stoichiometry: 1.0
species: 562732
type: SpeciesReference

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

493124
stoichiometry: 1.0
species: 562293
type: SpeciesReference

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

492967
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
type: KineticLaw

172939
units: 491513
value: 0.0
type: LocalParameter

492094
stoichiometry: 1.0
species: 562652
type: SpeciesReference

563812
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
type: Reaction

563113
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
type: Reaction

562632
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 561853
type: Species

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

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

563513
kinetic law: 493016
product: 493004
product: 492991
reactant: 492979
fast: false
reversible: false
type: Reaction

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

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

494309
stoichiometry: 1.0
species: 562633
type: SpeciesReference

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

563292
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
type: Reaction

563532
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
type: Reaction

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

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

493173
stoichiometry: 1.0
species: 562353
type: SpeciesReference

492844
stoichiometry: 1.0
species: 562233
type: SpeciesReference

563112
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
type: Reaction

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

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

492930
stoichiometry: 1.0
species: 562213
type: SpeciesReference

494153
stoichiometry: 1.0
species: 562573
type: SpeciesReference

493862
stoichiometry: 1.0
species: 562153
type: SpeciesReference