171413
stoichiometry: 1.0
species: 884388
type: SpeciesReference

170429
stoichiometry: 1.0
species: 883108
type: SpeciesReference

883508
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

885148
kinetic law: 171637
product: 171625
reactant: 171613
reactant: 171600
notes: Rate consts same as for MAPKKtyr.
fast: false
reversible: true
type: Reaction

195802
units: 169930
value: 6.0E-12
type: LocalParameter

884528
kinetic law: 170283
product: 170271
reactant: 170258
notes: Assume slowish too. Schaechter and Benowitz
fast: false
reversible: true
type: Reaction

195736
units: 169930
value: 4.0E-12
type: LocalParameter

173246
stoichiometry: 1.0
species: 884348
type: SpeciesReference

883048
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.02
initial amount: NaN
in compartment: 882928
type: Species

195820
units: 169930
value: 4.8E-10
type: LocalParameter

173766
local parameters: 195826
local parameters: 195825
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

195746
units: 169930
value: 4.2E-13
type: LocalParameter

172276
stoichiometry: 1.0
species: 883268
type: SpeciesReference

170087
stoichiometry: 1.0
species: 884268
type: SpeciesReference

195676
units: 169966
value: 6.0E-16
type: LocalParameter

884508
kinetic law: 170246
product: 170233
reactant: 170220
reactant: 170207
notes: Schaechter and Benowitz We have to increase Kf for conc scaling Changed kf to 2e-9 on Sept 19, 94. This gives better match.
fast: false
reversible: true
type: Reaction

885168
kinetic law: 171685
product: 171673
product: 171661
reactant: 171649
fast: false
reversible: false
type: Reaction

172349
stoichiometry: 1.0
species: 883648
type: SpeciesReference

170574
local parameters: 195687
local parameters: 195685
notes: kf*MAPK_slash_MKP_minus_1_star__star_-kb*MAPK_slash_Ubiquitination
type: KineticLaw

171514
stoichiometry: 1.0
species: 883368
type: SpeciesReference

173331
local parameters: 195809
notes: k3*PLA2_slash_PIP2_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

195755
units: 169930
value: 1.05E-13
type: LocalParameter

173670
local parameters: 195823
local parameters: 195822
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

173586
stoichiometry: 1.0
species: 884068
type: SpeciesReference

884668
kinetic law: 170574
product: 170562
reactant: 170550
notes: 3 Feb 2000. Rate of turnover of phosph form of MKP1 is from Brondello et al Science 286:2514 1999. Tau is about 150 min though it is not a clean exp falloff.
fast: false
reversible: true
type: Reaction

173428
local parameters: 195814
notes: k3*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

195821
units: 169930
value: 1.2E-10
type: LocalParameter

884648
kinetic law: 170538
product: 170526
reactant: 170514
notes: 3 Feb 2000. The levels of basal MAPK are so low that we need to have a basal mechanism for making MKP-1. This is easy, as the degradation tau is 45 min and basal MKP-1 levels are 2.4 nM in our model. x * 1 uM = 2.4e-3 * 0.37e-3 = 8.9e-7 May 30 2k. Basal levels shifted up a bit. kf now 1.0e-6 Jun 3 2k: kf now 8e-7 Jun 4 2k: kf = 7e-7
fast: false
reversible: true
type: Reaction

171745
stoichiometry: 1.0
species: 883468
type: SpeciesReference

885188
kinetic law: 171733
product: 171721
reactant: 171709
reactant: 171697
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

172592
stoichiometry: 1.0
species: 883728
type: SpeciesReference

170502
local parameters: 195682
local parameters: 195681
notes: kf*MKP_minus_1-kb*MAPK_slash_Ubiquitination
type: KineticLaw

171328
stoichiometry: 1.0
species: 883208
type: SpeciesReference

195687
units: 169930
value: 0.0
type: LocalParameter

171463
stoichiometry: 1.0
species: 884128
type: SpeciesReference

172532
stoichiometry: 1.0
species: 883568
type: SpeciesReference

173718
local parameters: 195824
notes: k3*Ras_slash_GEF_star__slash_GEF_star__minus_act_minus_ras_slash_GEF_star__minus_act_minus_ras_cplx
type: KineticLaw

883808
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

195811
units: 169966
value: 9.0E-12
type: LocalParameter

170949
stoichiometry: 1.0
species: 884008
type: SpeciesReference

195738
units: 169930
value: 6.0E-13
type: LocalParameter

170271
stoichiometry: 1.0
species: 882968
type: SpeciesReference

173258
stoichiometry: 1.0
species: 883928
type: SpeciesReference

885208
kinetic law: 171781
product: 171769
product: 171757
reactant: 171745
fast: false
reversible: false
type: Reaction

195744
units: 169966
value: 3.3E-12
type: LocalParameter

170417
local parameters: 195678
local parameters: 195676
notes: kf*PKC_slash_PKC_minus_cytosolic*DAG-kb*PKC_slash_PKC_minus_DAG
type: KineticLaw

170562
stoichiometry: 1.0
species: 884328
type: SpeciesReference

885768
kinetic law: 173138
product: 173126
product: 173114
reactant: 173102
fast: false
reversible: false
type: Reaction

171450
stoichiometry: 1.0
species: 883228
type: SpeciesReference

172252
stoichiometry: 1.0
species: 883608
type: SpeciesReference

171501
stoichiometry: 1.0
species: 883308
type: SpeciesReference

195674
units: 169966
value: 1.2E-16
type: LocalParameter

171425
stoichiometry: 1.0
species: 883228
type: SpeciesReference

195822
units: 169966
value: 1.98E-13
type: LocalParameter

172457
local parameters: 195775
notes: k3*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx
type: KineticLaw

173778
stoichiometry: 1.0
species: 884248
type: SpeciesReference

170099
stoichiometry: 1.0
species: 882948
type: SpeciesReference

195688
units: 169930
value: 1.0E-16
type: LocalParameter

172264
local parameters: 195767
notes: k3*MAPK_slash_nuc_MAPK_star__slash_MKP_minus_1_minus_synthesis_slash_MKP_minus_1_minus_synthesis_cplx
type: KineticLaw

195800
units: 169966
value: 1.98E-12
type: LocalParameter

195737
units: 169966
value: 1.62E-11
type: LocalParameter

195801
units: 169930
value: 2.5E-11
type: LocalParameter

173416
stoichiometry: 1.0
species: 883968
type: SpeciesReference

883908
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

883248
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.2
initial amount: NaN
in compartment: 882928
type: Species

171070
stoichiometry: 1.0
species: 883868
type: SpeciesReference

173343
stoichiometry: 1.0
species: 884348
type: SpeciesReference

195823
units: 169930
value: 8.0E-14
type: LocalParameter

173574
local parameters: 195820
local parameters: 195819
notes: k1*PLA2_slash_APC*PLA2_slash_PLA2_star__minus_Ca-k2*PLA2_slash_PLA2_star__minus_Ca_slash_kenz_slash_kenz_cplx
type: KineticLaw

172191
stoichiometry: 1.0
species: 883608
type: SpeciesReference

195723
units: 169930
value: 1.6E-11
type: LocalParameter

173706
stoichiometry: 1.0
species: 884128
type: SpeciesReference

195675
units: 169930
value: 1.0E-13
type: LocalParameter

171757
stoichiometry: 1.0
species: 883428
type: SpeciesReference

195757
units: 169966
value: 3.3E-12
type: LocalParameter

886048
kinetic law: 173814
product: 173802
product: 173790
reactant: 173778
fast: false
reversible: false
type: Reaction

170514
stoichiometry: 1.0
species: 884308
type: SpeciesReference

195689
units: 169930
value: 0.0
type: LocalParameter

195806
units: 169930
value: 5.4E-12
type: LocalParameter

172969
stoichiometry: 1.0
species: 883768
type: SpeciesReference

172445
stoichiometry: 1.0
species: 883648
type: SpeciesReference

171437
local parameters: 195734
local parameters: 195733
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

885488
kinetic law: 172457
product: 172445
product: 172433
reactant: 172421
fast: false
reversible: false
type: Reaction

195732
units: 169930
value: 4.0E-12
type: LocalParameter

883788
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

195722
units: 169966
value: 3.0E-13
type: LocalParameter

883988
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

170283
local parameters: 195671
local parameters: 195669
notes: kf*PKC_slash_PKC_minus_DAG_minus_AA-kb*PKC_slash_PKC_minus_DAG_minus_AA_star_
type: KineticLaw

883188
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

170683
local parameters: 195693
local parameters: 195692
notes: kf*MAPK_slash_MKP_minus_1_star__star_-kb*MAPK_slash_MKP_minus_1_minus_ser359_star_
type: KineticLaw

885288
kinetic law: 171974
product: 171962
product: 171950
reactant: 171938
fast: false
reversible: false
type: Reaction

170925
stoichiometry: 1.0
species: 884268
type: SpeciesReference

172640
stoichiometry: 1.0
species: 883648
type: SpeciesReference

195807
units: 169966
value: 2.76E-12
type: LocalParameter

172556
local parameters: 195780
notes: k3*MAPK_star__slash_MKP_minus_1_minus_phosph_slash_MKP_minus_1_minus_phosph_cplx
type: KineticLaw

170207
stoichiometry: 1.0
species: 882948
type: SpeciesReference

884868
kinetic law: 170997
product: 170985
reactant: 170973
notes: I need to check if the AA degradation pathway really leads back to APC. Anyway, it is a convenient buffered pool to dump it back into. For the purposes of the full model we use a rate of degradation of 0.2/sec Raised decay to 0.4 : see PLA35.g notes for Feb17
fast: false
reversible: true
type: Reaction

195731
units: 169930
value: 1.6E-11
type: LocalParameter

173355
stoichiometry: 1.0
species: 883968
type: SpeciesReference

885748
kinetic law: 173090
product: 173077
reactant: 173065
reactant: 173053
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

883588
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

173562
stoichiometry: 1.0
species: 884068
type: SpeciesReference

195759
units: 169930
value: 4.2E-13
type: LocalParameter

170404
stoichiometry: 1.0
species: 883108
type: SpeciesReference

885948
kinetic law: 173574
product: 173562
reactant: 173550
reactant: 173538
notes: This form should be 3 to 6 times as fast as the Ca-only form. I have scaled by 4x which seems to give a 5x rise. 10x raise Oct 22 12 x oct 24, changed k2 = 4 * k3
fast: false
reversible: true
type: Reaction

195749
units: 169966
value: 3.3E-12
type: LocalParameter

171721
stoichiometry: 1.0
species: 883468
type: SpeciesReference

195721
units: 169930
value: 0.0
type: LocalParameter

173610
stoichiometry: 1.0
species: 884048
type: SpeciesReference

171082
local parameters: 195714
local parameters: 195712
notes: kf*PLA2_slash_PLA2_star_-kb*PLA2_slash_PLA2_minus_cytosolic
type: KineticLaw

884128
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

195698
units: 169930
value: 5.0E-13
type: LocalParameter

172433
stoichiometry: 1.0
species: 884088
type: SpeciesReference

883888
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

885128
kinetic law: 171588
product: 171576
product: 171564
reactant: 171552
fast: false
reversible: false
type: Reaction

171488
local parameters: 195736
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_GEF_slash_PKC_minus_act_minus_GEF_cplx
type: KineticLaw

195804
units: 169966
value: 1.35E-12
type: LocalParameter

884488
kinetic law: 170195
product: 170183
reactant: 170171
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

172288
stoichiometry: 1.0
species: 883648
type: SpeciesReference

883108
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.16101666666667E-16
initial amount: NaN
in compartment: 882928
type: Species

884468
kinetic law: 170159
product: 170147
reactant: 170135
fast: false
reversible: true
type: Reaction

170307
stoichiometry: 1.0
species: 883048
type: SpeciesReference

171095
stoichiometry: 1.0
species: 884128
type: SpeciesReference

885808
kinetic law: 173234
product: 173222
product: 173210
reactant: 173198
fast: false
reversible: false
type: Reaction

883128
constant: false
boundary condition: false
has only substance units: false
initial concentration: 2.51883333333333E-19
initial amount: NaN
in compartment: 882928
type: Species

195734
units: 169930
value: 1.6E-11
type: LocalParameter

195678
units: 169930
value: 1.0E-13
type: LocalParameter

170295
stoichiometry: 1.0
species: 883148
type: SpeciesReference

884148
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

885108
kinetic law: 171540
product: 171527
reactant: 171514
reactant: 171501
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

195699
units: 169966
value: 1.00002E-12
type: LocalParameter

172544
stoichiometry: 1.0
species: 883648
type: SpeciesReference

171475
stoichiometry: 1.0
species: 884388
type: SpeciesReference

884768
kinetic law: 170768
product: 170756
reactant: 170744
reactant: 170731
notes: Assume binding is fast and limited only by available Ras*. 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 raise kb 4x to 4e-5 This step needed to memb-anchor and activate Raf: Leevers et al Nature 369 411-414.
fast: false
reversible: true
type: Reaction

885848
kinetic law: 173331
product: 173319
product: 173307
reactant: 173294
fast: false
reversible: false
type: Reaction

885428
kinetic law: 172313
product: 172300
reactant: 172288
reactant: 172276
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

170671
stoichiometry: 1.0
species: 883568
type: SpeciesReference

170937
stoichiometry: 1.0
species: 883888
type: SpeciesReference

171733
local parameters: 195746
local parameters: 195744
notes: k1*MAPK_slash_MAPKK*MAPK_slash_Raf_minus_GTP_minus_Ras_star_-k2*MAPK_slash_Raf_minus_GTP_minus_Ras_star__slash_Raf_minus_GTP_minus_Ras_star__dot_1_slash_Raf_minus_GTP_minus_Ras_star__dot_1_cplx
type: KineticLaw

883168
constant: false
boundary condition: false
has only substance units: false
initial concentration: 6.12
initial amount: NaN
in compartment: 882928
type: Species

195658
units: 169966
value: 6.0E-13
type: LocalParameter

195805
units: 169930
value: 2.16E-11
type: LocalParameter

884428
kinetic law: 170075
product: 170063
reactant: 170051
reactant: 170039
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

172580
stoichiometry: 1.0
species: 883648
type: SpeciesReference

883848
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

883148
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 882928
type: Species

173550
stoichiometry: 1.0
species: 884048
type: SpeciesReference

173622
local parameters: 195821
notes: k3*PLA2_slash_PLA2_star__minus_Ca_slash_kenz_slash_kenz_cplx
type: KineticLaw

171661
stoichiometry: 1.0
species: 883648
type: SpeciesReference

884448
kinetic law: 170123
product: 170111
reactant: 170099
reactant: 170087
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

195733
units: 169966
value: 6.0E-12
type: LocalParameter

173367
stoichiometry: 1.0
species: 883988
type: SpeciesReference

195679
units: 169966
value: 1.8E-14
type: LocalParameter

195747
units: 169930
value: 1.05E-13
type: LocalParameter

885408
kinetic law: 172264
product: 172252
product: 172239
reactant: 172227
fast: false
reversible: false
type: Reaction

195667
units: 169966
value: 1.2E-15
type: LocalParameter

169906
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

171034
stoichiometry: 1.0
species: 884048
type: SpeciesReference

195792
units: 169966
value: 1.98E-12
type: LocalParameter

172071
local parameters: 195760
notes: k3*MAPK_slash_RGR_slash_RGR_dot_2_slash_RGR_dot_2_cplx
type: KineticLaw

170901
stoichiometry: 1.0
species: 883968
type: SpeciesReference

171926
local parameters: 195754
local parameters: 195753
notes: k1*MAPK_slash_MAPKK*MAPK_slash_RGR-k2*MAPK_slash_RGR_slash_RGR_dot_1_slash_RGR_dot_1_cplx
type: KineticLaw

884048
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

170997
local parameters: 195709
local parameters: 195708
notes: kf*AA-kb*PLA2_slash_APC
type: KineticLaw

195666
units: 169930
value: 1.0E-13
type: LocalParameter

195791
units: 169930
value: 6.0E-12
type: LocalParameter

885088
kinetic law: 171488
product: 171475
product: 171463
reactant: 171450
fast: false
reversible: false
type: Reaction

885008
kinetic law: 171290
product: 171278
product: 171265
reactant: 171253
fast: false
reversible: false
type: Reaction

170368
local parameters: 195675
local parameters: 195674
notes: kf*AA*PKC_slash_PKC_minus_cytosolic-kb*PKC_slash_PKC_minus_AA_star_
type: KineticLaw

172665
stoichiometry: 1.0
species: 883348
type: SpeciesReference

170027
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

170587
stoichiometry: 1.0
species: 883568
type: SpeciesReference

170816
local parameters: 195700
local parameters: 195699
notes: kf*PLA2_slash_PLA2_minus_cytosolic*Ca-kb*PLA2_slash_PLA2_minus_Ca_star_
type: KineticLaw

173029
stoichiometry: 1.0
species: 883768
type: SpeciesReference

170635
stoichiometry: 1.0
species: 883748
type: SpeciesReference

195794
units: 169930
value: 6.0E-12
type: LocalParameter

883468
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

195730
units: 169966
value: 6.0E-12
type: LocalParameter

170985
stoichiometry: 1.0
species: 884348
type: SpeciesReference

883448
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

195808
units: 169930
value: 4.416E-11
type: LocalParameter

885788
kinetic law: 173186
product: 173174
reactant: 173162
reactant: 173150
notes: 10 x raise oct22 12 x oct 24, set k2 = 4 * k3
fast: false
reversible: true
type: Reaction

172397
stoichiometry: 1.0
species: 883688
type: SpeciesReference

170478
stoichiometry: 1.0
species: 883748
type: SpeciesReference

195669
units: 169930
value: 2.0E-12
type: LocalParameter

885588
kinetic law: 172703
modifier: 172690
product: 172677
reactant: 172665
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: false
type: Reaction

170913
local parameters: 195705
local parameters: 195703
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star_
type: KineticLaw

171938
stoichiometry: 1.0
species: 883528
type: SpeciesReference

883268
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

170829
stoichiometry: 1.0
species: 884368
type: SpeciesReference

883928
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

170695
stoichiometry: 1.0
species: 883648
type: SpeciesReference

172652
local parameters: 195783
notes: k3*MAPK_star__slash_MKP_minus_1_minus_phosph2_slash_MKP_minus_1_minus_phosph2_cplx
type: KineticLaw

195793
units: 169930
value: 2.5E-11
type: LocalParameter

173210
stoichiometry: 1.0
species: 883168
type: SpeciesReference

884708
kinetic law: 170647
product: 170635
reactant: 170623
notes: 24 Apr 2K: Based on 12 Feb 2K: Scaled up 10x so kf=0.01, kb=0
fast: false
reversible: true
type: Reaction

883228
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

195668
units: 169930
value: 1.0E-13
type: LocalParameter

171193
local parameters: 195721
local parameters: 195719
notes: kf*Ras_slash_GAP_star_-kb*Ras_slash_GAP
type: KineticLaw

195710
units: 169966
value: 6.0E-12
type: LocalParameter

171986
stoichiometry: 1.0
species: 883428
type: SpeciesReference

172313
local parameters: 195771
local parameters: 195769
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

884248
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

170051
stoichiometry: 1.0
species: 884288
type: SpeciesReference

170599
stoichiometry: 1.0
species: 884328
type: SpeciesReference

170647
local parameters: 195691
local parameters: 195690
notes: kf*MAPK_slash_MKP_minus_1_minus_ser359_star_-kb*MKP_minus_1
type: KineticLaw

886028
kinetic law: 173766
product: 173754
reactant: 173742
reactant: 173730
notes: From Eccleston et al JBC 268(36)pp27012-19 get Kd < 2uM, kcat - 10/sec From Martin et al Cell 63 843-849 1990 get Kd ~ 250 nM, kcat = 20/min I will go with the Eccleston figures as there are good error bars (10%). In general the values are reasonably close. k1 = 1.666e-3/sec, k2 = 1000/sec, k3 = 10/sec (note k3 is rate-limiting)
fast: false
reversible: true
type: Reaction

172957
stoichiometry: 1.0
species: 883428
type: SpeciesReference

885888
kinetic law: 173428
product: 173416
product: 173404
reactant: 173392
fast: false
reversible: false
type: Reaction

195809
units: 169930
value: 1.104E-11
type: LocalParameter

885228
kinetic law: 171829
product: 171817
reactant: 171805
reactant: 171793
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

171769
stoichiometry: 1.0
species: 883448
type: SpeciesReference

173294
stoichiometry: 1.0
species: 883948
type: SpeciesReference

883568
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

173404
stoichiometry: 1.0
species: 883168
type: SpeciesReference

885968
kinetic law: 173622
product: 173610
product: 173598
reactant: 173586
fast: false
reversible: false
type: Reaction

195701
units: 169966
value: 1.2E-15
type: LocalParameter

195711
units: 169930
value: 1.0E-13
type: LocalParameter

195663
units: 169930
value: 1.2705E-12
type: LocalParameter

883968
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

195742
units: 169930
value: 1.5E-13
type: LocalParameter

883308
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.36
initial amount: NaN
in compartment: 882928
type: Species

170973
stoichiometry: 1.0
species: 883168
type: SpeciesReference

195782
units: 169930
value: 4.0E-12
type: LocalParameter

882948
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.72083333333333E-17
initial amount: NaN
in compartment: 882928
type: Species

173694
stoichiometry: 1.0
species: 884168
type: SpeciesReference

171058
stoichiometry: 1.0
species: 884088
type: SpeciesReference

195752
units: 169930
value: 1.05E-13
type: LocalParameter

170344
stoichiometry: 1.0
species: 883148
type: SpeciesReference

171901
stoichiometry: 1.0
species: 883508
type: SpeciesReference

884388
constant: false
boundary condition: true
has only substance units: false
initial concentration: 2.12216666666667E-16
initial amount: NaN
in compartment: 882928
type: Species

170003
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

170550
stoichiometry: 1.0
species: 883588
type: SpeciesReference

195712
units: 169930
value: 1.7E-13
type: LocalParameter

170063
stoichiometry: 1.0
species: 882948
type: SpeciesReference

885268
kinetic law: 171926
product: 171914
reactant: 171901
reactant: 171889
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

171388
local parameters: 195732
notes: k3*PKC_minus_active_slash_PKC_minus_inact_minus_GAP_slash_PKC_minus_inact_minus_GAP_cplx
type: KineticLaw

172921
stoichiometry: 1.0
species: 883428
type: SpeciesReference

170611
local parameters: 195689
local parameters: 195688
notes: kf*MAPK_slash_MKP_minus_1_minus_ser359_star_-kb*MAPK_slash_Ubiquitination
type: KineticLaw

885388
kinetic law: 172215
product: 172203
reactant: 172191
reactant: 172179
notes: 5 Feb 2000 This is a crude model of activation of MKP1 production by MAPK. Time-course poorly constrained: 10 min to > 100 min. Rates are further constrained by the known degradation rates of MKP-1, also in this model. Peak MKP-1 is about 10 times basal (from Brondello et al Science 286:2514 1999). Max MAPK ~.25 uM, degradation 45 min. So this enz has to provide 22nM MKP every 45 min.
fast: false
reversible: true
type: Reaction

884908
kinetic law: 171082
product: 171070
reactant: 171058
fast: false
reversible: true
type: Reaction

171021
stoichiometry: 1.0
species: 884288
type: SpeciesReference

195662
units: 169930
value: 8.6348E-12
type: LocalParameter

172325
stoichiometry: 1.0
species: 883668
type: SpeciesReference

195741
units: 169930
value: 6.0E-13
type: LocalParameter

173319
stoichiometry: 1.0
species: 883928
type: SpeciesReference

885928
kinetic law: 173526
product: 173514
product: 173502
reactant: 173490
fast: false
reversible: false
type: Reaction

885368
kinetic law: 172167
modifier: 172155
product: 172143
reactant: 172131
notes: 3 Feb 2000. Same rates as MKP1
fast: false
reversible: false
type: Reaction

195781
units: 169966
value: 1.95E-13
type: LocalParameter

195702
units: 169930
value: 5.0E-13
type: LocalParameter

173222
stoichiometry: 1.0
species: 883888
type: SpeciesReference

195751
units: 169930
value: 4.2E-13
type: LocalParameter

169918
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

885308
kinetic law: 172023
product: 172011
reactant: 171999
reactant: 171986
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

195790
units: 169930
value: 2.5E-11
type: LocalParameter

171914
stoichiometry: 1.0
species: 883528
type: SpeciesReference

884308
notes: 3 Feb 2000. This represents the formation of MKP-1 when MAPK is stimulated. Concentration is pretty irrelevant here, set to 1 uM for convenience.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 882928
type: Species

173814
local parameters: 195828
notes: k3*Ras_slash_GAP_slash_GAP_minus_inact_minus_ras_slash_GAP_minus_inact_minus_ras_cplx
type: KineticLaw

172300
stoichiometry: 1.0
species: 883668
type: SpeciesReference

195665
units: 169930
value: 1.0E-12
type: LocalParameter

173282
local parameters: 195808
local parameters: 195807
notes: k1*PLA2_slash_APC*PLA2_slash_PIP2_minus_PLA2_star_-k2*PLA2_slash_PIP2_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

884988
kinetic law: 171241
product: 171229
reactant: 171217
reactant: 171205
notes: Rate consts from Chen et al Biochem 32, 1032 (1993) k3 = k2 = 4 k1 = 9e-5 Lower k1 to 1e-6 to balance 10X DAG sensitivity of PKC 11 May2K: Double Vmax. rates=1e-6, 32,8 29 May 2k: Vmax * 0.6. Rates=6e-7, 19.2, 4.8 30 May 2k: vmax=5. Rates=6.25e-7,20,5 3 Jun 2k: vmax=4. Rates=5e-7,16,4
fast: false
reversible: true
type: Reaction

195780
units: 169930
value: 1.0E-12
type: LocalParameter

171046
local parameters: 195711
local parameters: 195710
notes: kf*PLA2_slash_PLA2_star_*Ca-kb*PLA2_slash_PLA2_star__minus_Ca
type: KineticLaw

884328
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

884788
kinetic law: 170816
product: 170804
reactant: 170792
reactant: 170780
notes: Leslie and Channon BBA 1045 (1990) 261-270 fig6 pp267.
fast: false
reversible: true
type: Reaction

195740
units: 169966
value: 1.62E-11
type: LocalParameter

171841
stoichiometry: 1.0
species: 883488
type: SpeciesReference

173682
stoichiometry: 1.0
species: 884148
type: SpeciesReference

885828
kinetic law: 173282
product: 173270
reactant: 173258
reactant: 173246
notes: 10 X raise oct 22 12 X further raise oct 24 to allow for correct conc of enzyme
fast: false
reversible: true
type: Reaction

195754
units: 169930
value: 4.2E-13
type: LocalParameter

171302
stoichiometry: 1.0
species: 884228
type: SpeciesReference

170961
local parameters: 195707
local parameters: 195706
notes: kf*DAG*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_DAG_minus_Ca_minus_PLA2_star_
type: KineticLaw

195700
units: 169930
value: 1.0E-13
type: LocalParameter

170804
stoichiometry: 1.0
species: 883888
type: SpeciesReference

171376
stoichiometry: 1.0
species: 884388
type: SpeciesReference

170623
stoichiometry: 1.0
species: 883568
type: SpeciesReference

172933
stoichiometry: 1.0
species: 883768
type: SpeciesReference

172677
stoichiometry: 1.0
species: 883308
type: SpeciesReference

195664
units: 169930
value: 3.5026E-12
type: LocalParameter

170356
stoichiometry: 1.0
species: 883068
type: SpeciesReference

171108
stoichiometry: 1.0
species: 884108
type: SpeciesReference

884368
notes: This isn\'t explicitly present in the M&L model, but is obviously needed. I assume its conc is fixed at 1uM for now, which is a bit high. PLA2 is stim 7x by PIP2 @ 0.5 uM (Leslie and Channon BBA 1045:261(1990) Leslie and Channon say PIP2 is present at 0.1 - 0.2mol% range in membs, which comes to 50 nM. Ref is Majerus et al Cell 37 pp 701-703 1984 Lets use a lower level of 30 nM, same ref....
constant: true
boundary condition: true
has only substance units: false
initial concentration: 2.5
initial amount: NaN
in compartment: 882928
type: Species

171315
stoichiometry: 1.0
species: 884388
type: SpeciesReference

170075
local parameters: 195660
local parameters: 195658
notes: kf*PKC_slash_PKC_minus_cytosolic*Ca-kb*PKC_slash_PKC_minus_Ca
type: KineticLaw

885508
kinetic law: 172507
product: 172495
reactant: 172483
reactant: 172470
notes: 3 Feb 2000. See Brondello et al Science 286:2514 1999. Rates assumed standard MAPK rates based on Sanghera et al JBC 265(1):53-57 1990. 24 Apr 2K, based on 12 Feb 2K: scaled by 0.1 to 3.25e-7,4,1
fast: false
reversible: true
type: Reaction

173234
local parameters: 195806
notes: k3*PLA2_slash_PLA2_minus_Ca_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

195714
units: 169930
value: 0.0
type: LocalParameter

172604
local parameters: 195782
local parameters: 195781
notes: k1*MAPK_slash_MKP_minus_1_minus_ser359_star_*MAPK_star_-k2*MAPK_star__slash_MKP_minus_1_minus_phosph2_slash_MKP_minus_1_minus_phosph2_cplx
type: KineticLaw

884348
notes: arachodonylphosphatidylcholine is the favoured substrate from Wijkander and Sundler, JBC 202 pp 873-880, 1991. Their assay used 30 uM substrate, which is what the kinetics in this model are based on. For the later model we should locate a more realistic value for APC.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 30.0
initial amount: NaN
in compartment: 882928
type: Species

172337
stoichiometry: 1.0
species: 883328
type: SpeciesReference

173307
stoichiometry: 1.0
species: 883168
type: SpeciesReference

172860
stoichiometry: 1.0
species: 883368
type: SpeciesReference

883868
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.4
initial amount: NaN
in compartment: 882928
type: Species

195753
units: 169966
value: 3.3E-12
type: LocalParameter

170171
stoichiometry: 1.0
species: 883088
type: SpeciesReference

883648
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

195706
units: 169966
value: 3.0E-15
type: LocalParameter

173174
stoichiometry: 1.0
species: 883908
type: SpeciesReference

172011
stoichiometry: 1.0
species: 883548
type: SpeciesReference

883668
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

195773
units: 169966
value: 3.9E-12
type: LocalParameter

172727
stoichiometry: 1.0
species: 883348
type: SpeciesReference

170719
local parameters: 195696
local parameters: 195694
notes: kf*MAPK_star_-kb*MAPK_slash_nuc_MAPK_star_
type: KineticLaw

195716
units: 169930
value: 0.0
type: LocalParameter

886008
kinetic law: 173718
product: 173706
product: 173694
reactant: 173682
fast: false
reversible: false
type: Reaction

170159
local parameters: 195664
local parameters: 195663
notes: kf*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_memb_star_
type: KineticLaw

883688
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

195660
units: 169930
value: 5.0E-13
type: LocalParameter

173598
stoichiometry: 1.0
species: 883168
type: SpeciesReference

171352
stoichiometry: 1.0
species: 883208
type: SpeciesReference

195787
units: 169930
value: 1.0E-12
type: LocalParameter

884228
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.002
initial amount: NaN
in compartment: 882928
type: Species

171253
stoichiometry: 1.0
species: 883188
type: SpeciesReference

171576
stoichiometry: 1.0
species: 883368
type: SpeciesReference

885028
kinetic law: 171340
product: 171328
reactant: 171315
reactant: 171302
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

885528
kinetic law: 172556
product: 172544
product: 172532
reactant: 172519
fast: false
reversible: false
type: Reaction

883628
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

883088
constant: false
boundary condition: false
has only substance units: false
initial concentration: 8.46316666666667E-23
initial amount: NaN
in compartment: 882928
type: Species

885568
kinetic law: 172652
product: 172640
product: 172628
reactant: 172616
fast: false
reversible: false
type: Reaction

170865
local parameters: 195702
local parameters: 195701
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_cytosolic-kb*PLA2_slash_PIP2_minus_PLA2_star_
type: KineticLaw

170454
stoichiometry: 1.0
species: 883128
type: SpeciesReference

195774
units: 169930
value: 8.0E-11
type: LocalParameter

172812
stoichiometry: 1.0
species: 883788
type: SpeciesReference

195705
units: 169930
value: 1.0E-13
type: LocalParameter

885608
kinetic law: 172752
modifier: 172740
product: 172727
reactant: 172714
notes: See MKP1-tyr-deph
fast: false
reversible: false
type: Reaction

195715
units: 169930
value: 1.0E-12
type: LocalParameter

885068
kinetic law: 171437
product: 171425
reactant: 171413
reactant: 171400
notes: Rate consts from PKC-act-raf. This reaction activates GEF. Gives >= 2X stim of ras, and a 2X stim of MAPK over amount from direct phosph of c-raf. Note that it is a push-pull reaction, and also get eff through phosph and inact of GAPs.
fast: false
reversible: true
type: Reaction

195760
units: 169930
value: 1.05E-13
type: LocalParameter

173514
stoichiometry: 1.0
species: 884008
type: SpeciesReference

172203
stoichiometry: 1.0
species: 883628
type: SpeciesReference

195788
units: 169894
value: 0.0666666666666667
type: LocalParameter

883608
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

171168
stoichiometry: 1.0
species: 884208
type: SpeciesReference

884028
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

169978
exponent: 2.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

171865
stoichiometry: 1.0
species: 883448
type: SpeciesReference

195671
units: 169930
value: 2.0E-13
type: LocalParameter

195661
units: 169966
value: 7.9998E-15
type: LocalParameter

195771
units: 169930
value: 4.0E-11
type: LocalParameter

170768
local parameters: 195698
local parameters: 195697
notes: kf*MAPK_slash_craf_minus_1_star_*Ras_slash_GTP_minus_Ras-kb*MAPK_slash_Raf_minus_GTP_minus_Ras_star_
type: KineticLaw

171805
stoichiometry: 1.0
species: 883448
type: SpeciesReference

884268
notes: Baseline is 11.661 from running combined model to steady state. See ALL/NOTES for 23 Apr 1998.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 11.661
initial amount: NaN
in compartment: 882928
type: Species

170707
stoichiometry: 1.0
species: 883608
type: SpeciesReference

172179
stoichiometry: 1.0
species: 884308
type: SpeciesReference

170147
stoichiometry: 1.0
species: 883008
type: SpeciesReference

195718
units: 169930
value: 0.0
type: LocalParameter

170183
stoichiometry: 1.0
species: 883028
type: SpeciesReference

195761
units: 169930
value: 1.0E-12
type: LocalParameter

173186
local parameters: 195805
local parameters: 195804
notes: k1*PLA2_slash_APC*PLA2_slash_PLA2_minus_Ca_star_-k2*PLA2_slash_PLA2_minus_Ca_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

170233
stoichiometry: 1.0
species: 882988
type: SpeciesReference

171241
local parameters: 195723
local parameters: 195722
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

195789
units: 169966
value: 1.98E-12
type: LocalParameter

885248
kinetic law: 171877
product: 171865
product: 171853
reactant: 171841
fast: false
reversible: false
type: Reaction

171564
stoichiometry: 1.0
species: 883348
type: SpeciesReference

195672
units: 169930
value: 1.0E-12
type: LocalParameter

169954
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

171364
stoichiometry: 1.0
species: 884208
type: SpeciesReference

171950
stoichiometry: 1.0
species: 883428
type: SpeciesReference

195799
units: 169930
value: 6.0E-12
type: LocalParameter

195772
units: 169930
value: 1.0E-11
type: LocalParameter

170246
local parameters: 195668
local parameters: 195667
notes: kf*PKC_slash_PKC_minus_Ca*AA-kb*PKC_slash_PKC_minus_Ca_minus_AA_star_
type: KineticLaw

195703
units: 169966
value: 1.2E-14
type: LocalParameter

883328
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

173502
stoichiometry: 1.0
species: 883168
type: SpeciesReference

883528
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

884608
kinetic law: 170466
product: 170454
reactant: 170441
reactant: 170429
notes: Reduced kf to 0.66X to match Shinomura et al data. Initial: kf = 3.3333e-9 New: 2e-9 Newer: 2e-8 kb was 0.2 now 2.
fast: false
reversible: true
type: Reaction

170466
local parameters: 195680
local parameters: 195679
notes: kf*PKC_slash_PKC_minus_DAG*AA-kb*PKC_slash_PKC_minus_DAG_minus_AA
type: KineticLaw

195717
units: 169930
value: 1.0E-16
type: LocalParameter

170853
stoichiometry: 1.0
species: 883928
type: SpeciesReference

171853
stoichiometry: 1.0
species: 883368
type: SpeciesReference

172409
local parameters: 195774
local parameters: 195773
notes: k1*PLA2_slash_PLA2_minus_cytosolic*MAPK_star_-k2*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx
type: KineticLaw

195762
units: 169894
value: 0.0666666666666667
type: LocalParameter

172824
stoichiometry: 1.0
species: 883248
type: SpeciesReference

883948
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

883008
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.3896E-17
initial amount: NaN
in compartment: 882928
type: Species

884628
kinetic law: 170502
product: 170490
reactant: 170478
notes: 3 Feb 2000. Rate of turnover of non-phosph form of MKP1 is from Brondello et al Science 286:2514 1999. Tau is about 45 min.
fast: false
reversible: true
type: Reaction

885988
kinetic law: 173670
product: 173658
reactant: 173646
reactant: 173634
notes: Kinetics same as GEF-bg-act-ras
fast: false
reversible: true
type: Reaction

173270
stoichiometry: 1.0
species: 883948
type: SpeciesReference

883288
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.18
initial amount: NaN
in compartment: 882928
type: Species

195673
units: 169930
value: 5.0E-11
type: LocalParameter

884588
kinetic law: 170417
product: 170404
reactant: 170392
reactant: 170380
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

883548
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

171156
local parameters: 195718
local parameters: 195717
notes: kf*Ras_slash_GTP_minus_Ras-kb*Ras_slash_GDP_minus_Ras
type: KineticLaw

883348
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

169942
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

885448
kinetic law: 172361
product: 172349
product: 172337
reactant: 172325
fast: false
reversible: false
type: Reaction

195763
units: 169930
value: 1.0E-12
type: LocalParameter

173017
stoichiometry: 1.0
species: 883288
type: SpeciesReference

172628
stoichiometry: 1.0
species: 883588
type: SpeciesReference

171962
stoichiometry: 1.0
species: 883508
type: SpeciesReference

195777
units: 169966
value: 1.95E-13
type: LocalParameter

171552
stoichiometry: 1.0
species: 883388
type: SpeciesReference

172884
stoichiometry: 1.0
species: 883808
type: SpeciesReference

170039
stoichiometry: 1.0
species: 883148
type: SpeciesReference

170195
local parameters: 195666
local parameters: 195665
notes: kf*PKC_slash_PKC_minus_Ca_minus_DAG-kb*PKC_slash_PKC_minus_DAG_minus_memb_star_
type: KineticLaw

173150
stoichiometry: 1.0
species: 884348
type: SpeciesReference

172035
stoichiometry: 1.0
species: 883548
type: SpeciesReference

170756
stoichiometry: 1.0
species: 883448
type: SpeciesReference

195783
units: 169930
value: 1.0E-12
type: LocalParameter

885468
kinetic law: 172409
product: 172397
reactant: 172385
reactant: 172373
notes: Km = 25uM @ 50 uM ATP and 1mg/ml MBP (huge XS of substrate) Vmax = 4124 pmol/min/ml at a conc of 125 pmol/ml of enz, so: k3 = .5/sec (rate limiting) k1 = (k2 + k3)/Km = (.5 + 0)/(25*6e5) = 2e-8 (#/cell)^-1 #s from Sanghera et al JBC 265 pp 52 , 1990. From Nemenoff et al JBC 268(3):1960-1964 - using Sanghera\'s 1e-4 ratio of MAPK to protein, we get k3 = 7/sec from 1000 pmol/min/mg fig 5
fast: false
reversible: true
type: Reaction

171637
local parameters: 195741
local parameters: 195740
notes: k1*MAPK_slash_MAPK_minus_tyr*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx
type: KineticLaw

170135
stoichiometry: 1.0
species: 882948
type: SpeciesReference

172483
stoichiometry: 1.0
species: 883648
type: SpeciesReference

172703
local parameters: 195786
local parameters: 195785
notes: kcat*MKP_minus_1*MAPK_slash_MAPK_minus_tyr/(Km+MAPK_slash_MAPK_minus_tyr)
type: KineticLaw

884928
kinetic law: 171120
product: 171108
reactant: 171095
fast: false
reversible: true
type: Reaction

170332
stoichiometry: 1.0
species: 883168
type: SpeciesReference

173538
stoichiometry: 1.0
species: 884348
type: SpeciesReference

883488
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

195719
units: 169930
value: 1.0E-13
type: LocalParameter

195764
units: 169894
value: 0.0666666666666667
type: LocalParameter

884108
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.1
initial amount: NaN
in compartment: 882928
type: Species

195709
units: 169930
value: 0.0
type: LocalParameter

884968
kinetic law: 171193
product: 171180
reactant: 171168
notes: Assume a reasonably good rate for dephosphorylating it, 1/sec
fast: false
reversible: true
type: Reaction

171889
stoichiometry: 1.0
species: 883288
type: SpeciesReference

172083
stoichiometry: 1.0
species: 883348
type: SpeciesReference

172981
stoichiometry: 1.0
species: 883828
type: SpeciesReference

170841
stoichiometry: 1.0
species: 883868
type: SpeciesReference

173102
stoichiometry: 1.0
species: 883848
type: SpeciesReference

172714
stoichiometry: 1.0
species: 883648
type: SpeciesReference

882968
constant: false
boundary condition: false
has only substance units: false
initial concentration: 4.91366666666667E-18
initial amount: NaN
in compartment: 882928
type: Species

195798
units: 169930
value: 2.5E-11
type: LocalParameter

170220
stoichiometry: 1.0
species: 883168
type: SpeciesReference

173490
stoichiometry: 1.0
species: 884028
type: SpeciesReference

173065
stoichiometry: 1.0
species: 883768
type: SpeciesReference

171265
stoichiometry: 1.0
species: 883268
type: SpeciesReference

195765
units: 169966
value: 4.02E-17
type: LocalParameter

171709
stoichiometry: 1.0
species: 883448
type: SpeciesReference

171540
local parameters: 195738
local parameters: 195737
notes: k1*MAPK_slash_MAPK*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx
type: KineticLaw

172872
stoichiometry: 1.0
species: 883768
type: SpeciesReference

884828
kinetic law: 170913
product: 170901
reactant: 170889
reactant: 170877
fast: false
reversible: true
type: Reaction

884188
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.2
initial amount: NaN
in compartment: 882928
type: Species

173005
stoichiometry: 1.0
species: 883828
type: SpeciesReference

172616
stoichiometry: 1.0
species: 883728
type: SpeciesReference

170659
stoichiometry: 1.0
species: 883588
type: SpeciesReference

171340
local parameters: 195731
local parameters: 195730
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

172788
stoichiometry: 1.0
species: 883788
type: SpeciesReference

171290
local parameters: 195728
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_raf_slash_PKC_minus_act_minus_raf_cplx
type: KineticLaw

195775
units: 169930
value: 2.0E-11
type: LocalParameter

171974
local parameters: 195755
notes: k3*MAPK_slash_RGR_slash_RGR_dot_1_slash_RGR_dot_1_cplx
type: KineticLaw

195708
units: 169930
value: 4.0E-13
type: LocalParameter

170380
stoichiometry: 1.0
species: 883148
type: SpeciesReference

170320
local parameters: 195673
local parameters: 195672
notes: kf*PKC_slash_PKC_minus_cytosolic-kb*PKC_slash_PKC_minus_basal_star_
type: KineticLaw

884168
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

170744
stoichiometry: 1.0
species: 884168
type: SpeciesReference

885908
kinetic law: 173478
product: 173465
reactant: 173453
reactant: 173440
notes: 10 X raise oct 22 12 X raise oct 24 + conversion to k2 =4 * k3
fast: false
reversible: true
type: Reaction

170123
local parameters: 195662
local parameters: 195661
notes: kf*DAG*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_DAG
type: KineticLaw

171649
stoichiometry: 1.0
species: 883408
type: SpeciesReference

172495
stoichiometry: 1.0
species: 883708
type: SpeciesReference

173162
stoichiometry: 1.0
species: 883888
type: SpeciesReference

195785
units: 169930
value: 1.0E-12
type: LocalParameter

172023
local parameters: 195759
local parameters: 195757
notes: k1*MAPK_slash_MAPKK_minus_ser*MAPK_slash_RGR-k2*MAPK_slash_RGR_slash_RGR_dot_2_slash_RGR_dot_2_cplx
type: KineticLaw

195766
units: 169930
value: 1.0E-15
type: LocalParameter

171877
local parameters: 195752
notes: k3*MAPK_slash_Raf_minus_GTP_minus_Ras_star__slash_Raf_minus_GTP_minus_Ras_star__dot_2_slash_Raf_minus_GTP_minus_Ras_star__dot_2_cplx
type: KineticLaw

172095
stoichiometry: 1.0
species: 883308
type: SpeciesReference

171278
stoichiometry: 1.0
species: 884388
type: SpeciesReference

173526
local parameters: 195817
notes: k3*PLA2_slash_DAG_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

884068
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

195707
units: 169930
value: 4.0E-12
type: LocalParameter

195796
units: 169966
value: 1.98E-12
type: LocalParameter

882914
constant: true
size: 1.0E-18
spatial dimensions: 3.0
type: Compartment

172119
local parameters: 195762
local parameters: 195761
notes: kcat*MAPK_slash_MKP_minus_1_star__star_*MAPK_slash_MAPK_minus_tyr/(Km+MAPK_slash_MAPK_minus_tyr)
type: KineticLaw

173802
stoichiometry: 1.0
species: 884228
type: SpeciesReference

173077
stoichiometry: 1.0
species: 883848
type: SpeciesReference

171999
stoichiometry: 1.0
species: 883508
type: SpeciesReference

882928
constant: true
size: 1.0E-12
spatial dimensions: 3.0
type: Compartment

195786
units: 169894
value: 0.0666666666666667
type: LocalParameter

170441
stoichiometry: 1.0
species: 883168
type: SpeciesReference

170780
stoichiometry: 1.0
species: 883868
type: SpeciesReference

173646
stoichiometry: 1.0
species: 884128
type: SpeciesReference

195691
units: 169930
value: 0.0
type: LocalParameter

884728
kinetic law: 170683
product: 170671
reactant: 170659
notes: 24 Apr 2K, based on 12 Feb 2K: Scaled up 10x to kf=0.01, kb=0
fast: false
reversible: true
type: Reaction

195681
units: 169930
value: 3.7E-16
type: LocalParameter

883408
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

883828
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

884008
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

172568
stoichiometry: 1.0
species: 883568
type: SpeciesReference

195819
units: 169966
value: 3.0E-11
type: LocalParameter

171120
local parameters: 195716
local parameters: 195715
notes: kf*Ras_slash_GEF_star_-kb*Ras_slash_inact_minus_GEF
type: KineticLaw

884208
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

171217
stoichiometry: 1.0
species: 884388
type: SpeciesReference

883428
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

884748
kinetic law: 170719
product: 170707
reactant: 170695
notes: 5 Feb 2000. A nuclear translocation step. The rates are set up so that not too much MAPK gets siphoned off. 24 Apr 2000. Based on 12 Feb model. Rates slowed down x 0.02 to kf=2e-5 kb=1e-4
fast: false
reversible: true
type: Reaction

173392
stoichiometry: 1.0
species: 883988
type: SpeciesReference

170731
stoichiometry: 1.0
species: 883268
type: SpeciesReference

173126
stoichiometry: 1.0
species: 883768
type: SpeciesReference

169991
exponent: -1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

173465
stoichiometry: 1.0
species: 884028
type: SpeciesReference

172519
stoichiometry: 1.0
species: 883708
type: SpeciesReference

195767
units: 169930
value: 1.0E-16
type: LocalParameter

171400
stoichiometry: 1.0
species: 884108
type: SpeciesReference

885048
kinetic law: 171388
product: 171376
product: 171364
reactant: 171352
fast: false
reversible: false
type: Reaction

172059
stoichiometry: 1.0
species: 883508
type: SpeciesReference

171527
stoichiometry: 1.0
species: 883388
type: SpeciesReference

883068
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.81333333333333E-17
initial amount: NaN
in compartment: 882928
type: Species

195690
units: 169930
value: 1.0E-14
type: LocalParameter

885548
kinetic law: 172604
product: 172592
reactant: 172580
reactant: 172568
notes: 3 Feb 2000. See Brondello et al Science 286:2514 1999. Rates assumed standard MAPK rates based on Sanghera et al JBC 265(1):53-57 1990. 24 Apr 2K, based on 12 Feb 2K: Scaled x0.1 to 3.25e-7,4,1
fast: false
reversible: true
type: Reaction

172373
stoichiometry: 1.0
species: 883868
type: SpeciesReference

195680
units: 169930
value: 2.0E-12
type: LocalParameter

171613
stoichiometry: 1.0
species: 883368
type: SpeciesReference

170111
stoichiometry: 1.0
species: 883088
type: SpeciesReference

172143
stoichiometry: 1.0
species: 883348
type: SpeciesReference

171180
stoichiometry: 1.0
species: 884228
type: SpeciesReference

172776
stoichiometry: 1.0
species: 883768
type: SpeciesReference

170392
stoichiometry: 1.0
species: 884268
type: SpeciesReference

173790
stoichiometry: 1.0
species: 884188
type: SpeciesReference

173453
stoichiometry: 1.0
species: 884008
type: SpeciesReference

195828
units: 169930
value: 1.0E-11
type: LocalParameter

173730
stoichiometry: 1.0
species: 884168
type: SpeciesReference

195693
units: 169930
value: 0.0
type: LocalParameter

172470
stoichiometry: 1.0
species: 883748
type: SpeciesReference

885728
kinetic law: 173041
product: 173029
product: 173017
reactant: 173005
fast: false
reversible: false
type: Reaction

173053
stoichiometry: 1.0
species: 883328
type: SpeciesReference

195769
units: 169966
value: 1.95E-12
type: LocalParameter

195779
units: 169930
value: 4.0E-12
type: LocalParameter

173634
stoichiometry: 1.0
species: 884188
type: SpeciesReference

170792
stoichiometry: 1.0
species: 884288
type: SpeciesReference

883708
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

883728
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

195817
units: 169930
value: 6.0E-11
type: LocalParameter

172507
local parameters: 195779
local parameters: 195777
notes: k1*MKP_minus_1*MAPK_star_-k2*MAPK_star__slash_MKP_minus_1_minus_phosph_slash_MKP_minus_1_minus_phosph_cplx
type: KineticLaw

173114
stoichiometry: 1.0
species: 883268
type: SpeciesReference

173440
stoichiometry: 1.0
species: 884348
type: SpeciesReference

172239
stoichiometry: 1.0
species: 883748
type: SpeciesReference

171697
stoichiometry: 1.0
species: 883288
type: SpeciesReference

885708
kinetic law: 172993
product: 172981
reactant: 172969
reactant: 172957
fast: false
reversible: true
type: Reaction

171229
stoichiometry: 1.0
species: 883188
type: SpeciesReference

172385
stoichiometry: 1.0
species: 883648
type: SpeciesReference

171625
stoichiometry: 1.0
species: 883408
type: SpeciesReference

883768
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.224
initial amount: NaN
in compartment: 882928
type: Species

195692
units: 169930
value: 1.0E-14
type: LocalParameter

172131
stoichiometry: 1.0
species: 883648
type: SpeciesReference

172047
stoichiometry: 1.0
species: 883368
type: SpeciesReference

883028
constant: false
boundary condition: false
has only substance units: false
initial concentration: 9.43516666666667E-21
initial amount: NaN
in compartment: 882928
type: Species

195816
units: 169930
value: 2.4E-10
type: LocalParameter

172764
stoichiometry: 1.0
species: 883268
type: SpeciesReference

172421
stoichiometry: 1.0
species: 883688
type: SpeciesReference

884288
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.08
initial amount: NaN
in compartment: 882928
type: Species

883748
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0027
initial amount: NaN
in compartment: 882928
type: Species

884568
kinetic law: 170368
product: 170356
reactant: 170344
reactant: 170332
notes: Raise kf from 1.667e-10 to 2e-10 to get better match to data.
fast: false
reversible: true
type: Reaction

885868
kinetic law: 173380
product: 173367
reactant: 173355
reactant: 173343
notes: 10 x raise oct 22 12 x and rescale for k2 = 4 * k3 convention oct 24 Increase further to get the match to expt, which was spoilt due to large accumulation of PLA2 in the enzyme complexed forms. Lets raise k3, leaving the others at k1 = 1.5e-5 and k2 = 144 since they are large already.
fast: false
reversible: true
type: Reaction

171144
stoichiometry: 1.0
species: 884188
type: SpeciesReference

MODEL9071773985
reaction: 884908
reaction: 884788
species: 884388
reaction: 885588
reaction: 884808
reaction: 884748
name: Bhalla2001_MAPK_MKP1_oscillation
species: 882948
reaction: 884648
reaction: 884628
species: 883348
reaction: 885908
species: 884308
reaction: 884428
reaction: 885448
species: 883628
species: 883508
reaction: 885888
reaction: 885728
species: 883588
substance units: 170015
reaction: 885328
species: 883088
species: 883188
species: 884228
species: 883908
reaction: 885788
reaction: 885768
units def: 169966
species: 883568
reaction: 886048
reaction: 886028
reaction: 884928
species: 883848
species: 883028
reaction: 885188
reaction: 885168
reaction: 885828
reaction: 885808
reaction: 884688
species: 883308
reaction: 885128
species: 883008
species: 883108
species: 883768
reaction: 884768
species: 883368
reaction: 884728
species: 884268
reaction: 885068
species: 883528
reaction: 885048
species: 883288
species: 883988
reaction: 884608
reaction: 885428
species: 883948
species: 884168
reaction: 885748
rule: 884408
reaction: 885308
reaction: 885708
reaction: 884588
species: 883048
reaction: 884568
time units: 131570
reaction: 885288
reaction: 885268
species: 883468
reaction: 885248
area units: area
reaction: 885228
reaction: 885148
reaction: 885688
species: 883448
species: 882968
reaction: 885108
reaction: 885568
species: 884348
species: 883728

883368
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

171685
local parameters: 195742
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx
type: KineticLaw

170538
local parameters: 195684
local parameters: 195683
notes: kf*MAPK_slash_MKP_minus_1_minus_gene-kb*MKP_minus_1
type: KineticLaw

885688
kinetic law: 172945
product: 172933
product: 172921
reactant: 172909
fast: false
reversible: false
type: Reaction

195685
units: 169930
value: 1.0E-16
type: LocalParameter

882988
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.75E-16
initial amount: NaN
in compartment: 882928
type: Species

170889
stoichiometry: 1.0
species: 883888
type: SpeciesReference

195825
units: 169966
value: 9.996E-10
type: LocalParameter

172836
stoichiometry: 1.0
species: 883768
type: SpeciesReference

883208
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

885668
kinetic law: 172896
product: 172884
reactant: 172872
reactant: 172860
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

170258
stoichiometry: 1.0
species: 883128
type: SpeciesReference

172227
stoichiometry: 1.0
species: 883628
type: SpeciesReference

195739
units: 169930
value: 1.5E-13
type: LocalParameter

883388
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

195815
units: 169966
value: 1.5E-11
type: LocalParameter

195694
units: 169930
value: 2.0E-17
type: LocalParameter

172752
local parameters: 195788
local parameters: 195787
notes: kcat*MKP_minus_1*MAPK_star_/(Km+MAPK_star_)
type: KineticLaw

884948
kinetic law: 171156
product: 171144
reactant: 171132
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

171781
local parameters: 195747
notes: k3*MAPK_slash_Raf_minus_GTP_minus_Ras_star__slash_Raf_minus_GTP_minus_Ras_star__dot_1_slash_Raf_minus_GTP_minus_Ras_star__dot_1_cplx
type: KineticLaw

885628
kinetic law: 172800
product: 172788
reactant: 172776
reactant: 172764
notes: See parent PPhosphatase2A for parms
fast: false
reversible: true
type: Reaction

173754
stoichiometry: 1.0
species: 884248
type: SpeciesReference

885328
kinetic law: 172071
product: 172059
product: 172047
reactant: 172035
fast: false
reversible: false
type: Reaction

195684
units: 169930
value: 0.0
type: LocalParameter

885648
kinetic law: 172848
product: 172836
product: 172824
reactant: 172812
fast: false
reversible: false
type: Reaction

195824
units: 169930
value: 2.0E-14
type: LocalParameter

173198
stoichiometry: 1.0
species: 883908
type: SpeciesReference

170490
stoichiometry: 1.0
species: 884328
type: SpeciesReference

173478
local parameters: 195816
local parameters: 195815
notes: k1*PLA2_slash_APC*PLA2_slash_DAG_minus_Ca_minus_PLA2_star_-k2*PLA2_slash_DAG_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

171817
stoichiometry: 1.0
species: 883488
type: SpeciesReference

195814
units: 169930
value: 3.6E-11
type: LocalParameter

885348
kinetic law: 172119
modifier: 172107
product: 172095
reactant: 172083
notes: 3 Feb 2000. Same rates as MKP-1.
fast: false
reversible: false
type: Reaction

172167
local parameters: 195764
local parameters: 195763
notes: kcat*MAPK_slash_MKP_minus_1_star__star_*MAPK_star_/(Km+MAPK_star_)
type: KineticLaw

884688
kinetic law: 170611
product: 170599
reactant: 170587
notes: 3 Feb 2000. Rate of turnover of phosph form of MKP1 is from Brondello et al Science 286:2514 1999. Tau is about 150 min though it is not a clean exp falloff.
fast: false
reversible: true
type: Reaction

173658
stoichiometry: 1.0
species: 884148
type: SpeciesReference

195697
units: 169966
value: 2.4E-11
type: LocalParameter

170526
stoichiometry: 1.0
species: 883748
type: SpeciesReference

171673
stoichiometry: 1.0
species: 883368
type: SpeciesReference

195683
units: 169930
value: 7.0E-19
type: LocalParameter

171132
stoichiometry: 1.0
species: 884168
type: SpeciesReference

884848
kinetic law: 170961
product: 170949
reactant: 170937
reactant: 170925
notes: 27 June 1996 Scaled kf down by 0.015 from 3.33e-7 to 5e-9 to fit with revised DAG estimates and use of mole-fraction to calculate eff on PLA2.
fast: false
reversible: true
type: Reaction

171205
stoichiometry: 1.0
species: 883248
type: SpeciesReference

172909
stoichiometry: 1.0
species: 883808
type: SpeciesReference

173380
local parameters: 195813
local parameters: 195811
notes: k1*PLA2_slash_APC*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star_-k2*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

171600
stoichiometry: 1.0
species: 883348
type: SpeciesReference

884888
kinetic law: 171046
product: 171034
reactant: 171021
reactant: 171009
notes: To start off, same kinetics as the PLA2-Ca-act direct pathway. Oops ! Missed out the Ca input to this pathway first time round. Let\'s raise the forward rate about 3x to 5e-6. This will let us reduce the rather high rates we have used for the kenz on PLA2*-Ca. In fact, it may be that the rates are not that different, just that this pathway for getting the PLA2 to the memb is more efficien....
fast: false
reversible: true
type: Reaction

172215
local parameters: 195766
local parameters: 195765
notes: k1*MAPK_slash_MKP_minus_1_minus_gene*MAPK_slash_nuc_MAPK_star_-k2*MAPK_slash_nuc_MAPK_star__slash_MKP_minus_1_minus_synthesis_slash_MKP_minus_1_minus_synthesis_cplx
type: KineticLaw

170877
stoichiometry: 1.0
species: 884368
type: SpeciesReference

195813
units: 169930
value: 1.44E-10
type: LocalParameter

173742
stoichiometry: 1.0
species: 884228
type: SpeciesReference

884808
kinetic law: 170865
product: 170853
reactant: 170841
reactant: 170829
fast: false
reversible: true
type: Reaction

884088
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 882928
type: Species

195696
units: 169930
value: 1.0E-16
type: LocalParameter

171588
local parameters: 195739
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx
type: KineticLaw

195682
units: 169930
value: 0.0
type: LocalParameter

171793
stoichiometry: 1.0
species: 883428
type: SpeciesReference

884548
kinetic law: 170320
product: 170307
reactant: 170295
notes: Initial basal levels were set by kf = 1, kb = 20. In model, though, the basal levels of PKC activity are higher.
fast: false
reversible: true
type: Reaction

171009
stoichiometry: 1.0
species: 884088
type: SpeciesReference

195728
units: 169930
value: 4.0E-12
type: LocalParameter

195826
units: 169930
value: 1.0E-9
type: LocalParameter

171829
local parameters: 195751
local parameters: 195749
notes: k1*MAPK_slash_MAPKK_minus_ser*MAPK_slash_Raf_minus_GTP_minus_Ras_star_-k2*MAPK_slash_Raf_minus_GTP_minus_Ras_star__slash_Raf_minus_GTP_minus_Ras_star__dot_2_slash_Raf_minus_GTP_minus_Ras_star__dot_2_cplx
type: KineticLaw

172361
local parameters: 195772
notes: k3*MAPK_star__slash_MAPK_star__minus_feedback_slash_MAPK_star__minus_feedback_cplx
type: KineticLaw