MODEL9071773985
type: SBMLModel
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
length unit: length
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
reaction: 885228
reaction: 885148
reaction: 885688
species: 883448
species: 882968
reaction: 885108
reaction: 885568
species: 884348

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

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

195714
type: LocalParameter
units: 169930
value: 0.0

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

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

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

171070
type: SpeciesReference
stoichiometry: 1.0
species: 883868

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

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

171058
type: SpeciesReference
stoichiometry: 1.0
species: 884088

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

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

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

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

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

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

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

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

170804
type: SpeciesReference
stoichiometry: 1.0
species: 883888

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

170792
type: SpeciesReference
stoichiometry: 1.0
species: 884288

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

170780
type: SpeciesReference
stoichiometry: 1.0
species: 883868

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

885588
type: Reaction
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

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

195786
type: LocalParameter
units: 169894
value: 0.0666666666666667

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

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

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

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

172677
type: SpeciesReference
stoichiometry: 1.0
species: 883308

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

172665
type: SpeciesReference
stoichiometry: 1.0
species: 883348

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

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

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

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

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

170853
type: SpeciesReference
stoichiometry: 1.0
species: 883928

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

170841
type: SpeciesReference
stoichiometry: 1.0
species: 883868

170829
type: SpeciesReference
stoichiometry: 1.0
species: 884368

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

884748
type: Reaction
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

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

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

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

170707
type: SpeciesReference
stoichiometry: 1.0
species: 883608

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

170695
type: SpeciesReference
stoichiometry: 1.0
species: 883648

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

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

884648
type: Reaction
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

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

195684
type: LocalParameter
units: 169930
value: 0.0

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

170526
type: SpeciesReference
stoichiometry: 1.0
species: 883748

170514
type: SpeciesReference
stoichiometry: 1.0
species: 884308

884308
type: Species
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

884628
type: Reaction
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

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

195682
type: LocalParameter
units: 169930
value: 0.0

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

170490
type: SpeciesReference
stoichiometry: 1.0
species: 884328

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

170478
type: SpeciesReference
stoichiometry: 1.0
species: 883748

885908
type: Reaction
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

173478
type: KineticLaw
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

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

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

173465
type: SpeciesReference
stoichiometry: 1.0
species: 884028

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

173453
type: SpeciesReference
stoichiometry: 1.0
species: 884008

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

173440
type: SpeciesReference
stoichiometry: 1.0
species: 884348

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

884428
type: Reaction
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

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

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

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

170063
type: SpeciesReference
stoichiometry: 1.0
species: 882948

170051
type: SpeciesReference
stoichiometry: 1.0
species: 884288

170039
type: SpeciesReference
stoichiometry: 1.0
species: 883148

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

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

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

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

172349
type: SpeciesReference
stoichiometry: 1.0
species: 883648

172337
type: SpeciesReference
stoichiometry: 1.0
species: 883328

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

172325
type: SpeciesReference
stoichiometry: 1.0
species: 883668

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

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

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

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

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

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

173416
type: SpeciesReference
stoichiometry: 1.0
species: 883968

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

173404
type: SpeciesReference
stoichiometry: 1.0
species: 883168

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

173392
type: SpeciesReference
stoichiometry: 1.0
species: 883988

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

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

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

173029
type: SpeciesReference
stoichiometry: 1.0
species: 883768

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

173017
type: SpeciesReference
stoichiometry: 1.0
species: 883288

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

173005
type: SpeciesReference
stoichiometry: 1.0
species: 883828

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

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

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

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

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

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

172059
type: SpeciesReference
stoichiometry: 1.0
species: 883508

172047
type: SpeciesReference
stoichiometry: 1.0
species: 883368

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

172035
type: SpeciesReference
stoichiometry: 1.0
species: 883548

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

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

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

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

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

885788
type: Reaction
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

173186
type: KineticLaw
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

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

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

173174
type: SpeciesReference
stoichiometry: 1.0
species: 883908

173162
type: SpeciesReference
stoichiometry: 1.0
species: 883888

173150
type: SpeciesReference
stoichiometry: 1.0
species: 884348

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

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

173126
type: SpeciesReference
stoichiometry: 1.0
species: 883768

173114
type: SpeciesReference
stoichiometry: 1.0
species: 883268

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

173102
type: SpeciesReference
stoichiometry: 1.0
species: 883848

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

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

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

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

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

173802
type: SpeciesReference
stoichiometry: 1.0
species: 884228

173790
type: SpeciesReference
stoichiometry: 1.0
species: 884188

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

173778
type: SpeciesReference
stoichiometry: 1.0
species: 884248

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

886028
type: Reaction
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

173766
type: KineticLaw
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

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

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

173754
type: SpeciesReference
stoichiometry: 1.0
species: 884248

173742
type: SpeciesReference
stoichiometry: 1.0
species: 884228

173730
type: SpeciesReference
stoichiometry: 1.0
species: 884168

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

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

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

195716
type: LocalParameter
units: 169930
value: 0.0

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

171108
type: SpeciesReference
stoichiometry: 1.0
species: 884108

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

171095
type: SpeciesReference
stoichiometry: 1.0
species: 884128

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

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

885188
type: Reaction
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

171733
type: KineticLaw
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

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

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

171721
type: SpeciesReference
stoichiometry: 1.0
species: 883468

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

171709
type: SpeciesReference
stoichiometry: 1.0
species: 883448

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

171697
type: SpeciesReference
stoichiometry: 1.0
species: 883288

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

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

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

171673
type: SpeciesReference
stoichiometry: 1.0
species: 883368

171661
type: SpeciesReference
stoichiometry: 1.0
species: 883648

171649
type: SpeciesReference
stoichiometry: 1.0
species: 883408

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

885828
type: Reaction
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

173282
type: KineticLaw
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

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

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

173270
type: SpeciesReference
stoichiometry: 1.0
species: 883948

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

173258
type: SpeciesReference
stoichiometry: 1.0
species: 883928

173246
type: SpeciesReference
stoichiometry: 1.0
species: 884348

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

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

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

173222
type: SpeciesReference
stoichiometry: 1.0
species: 883888

173210
type: SpeciesReference
stoichiometry: 1.0
species: 883168

173198
type: SpeciesReference
stoichiometry: 1.0
species: 883908

884688
type: Reaction
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

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

195689
type: LocalParameter
units: 169930
value: 0.0

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

170599
type: SpeciesReference
stoichiometry: 1.0
species: 884328

170587
type: SpeciesReference
stoichiometry: 1.0
species: 883568

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

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

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

171576
type: SpeciesReference
stoichiometry: 1.0
species: 883368

171564
type: SpeciesReference
stoichiometry: 1.0
species: 883348

171552
type: SpeciesReference
stoichiometry: 1.0
species: 883388

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

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

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

884768
type: Reaction
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

170768
type: KineticLaw
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_

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

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

170756
type: SpeciesReference
stoichiometry: 1.0
species: 883448

170744
type: SpeciesReference
stoichiometry: 1.0
species: 884168

170731
type: SpeciesReference
stoichiometry: 1.0
species: 883268

884728
type: Reaction
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

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

195693
type: LocalParameter
units: 169930
value: 0.0

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

170671
type: SpeciesReference
stoichiometry: 1.0
species: 883568

170659
type: SpeciesReference
stoichiometry: 1.0
species: 883588

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

885068
type: Reaction
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

171437
type: KineticLaw
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

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

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

171425
type: SpeciesReference
stoichiometry: 1.0
species: 883228

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

171413
type: SpeciesReference
stoichiometry: 1.0
species: 884388

171400
type: SpeciesReference
stoichiometry: 1.0
species: 884108

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

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

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

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

171376
type: SpeciesReference
stoichiometry: 1.0
species: 884388

171364
type: SpeciesReference
stoichiometry: 1.0
species: 884208

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

171352
type: SpeciesReference
stoichiometry: 1.0
species: 883208

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

884608
type: Reaction
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

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

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

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

170454
type: SpeciesReference
stoichiometry: 1.0
species: 883128

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

170441
type: SpeciesReference
stoichiometry: 1.0
species: 883168

170429
type: SpeciesReference
stoichiometry: 1.0
species: 883108

885428
type: Reaction
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

172313
type: KineticLaw
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

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

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

172300
type: SpeciesReference
stoichiometry: 1.0
species: 883668

172288
type: SpeciesReference
stoichiometry: 1.0
species: 883648

172276
type: SpeciesReference
stoichiometry: 1.0
species: 883268

885748
type: Reaction
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

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

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

173077
type: SpeciesReference
stoichiometry: 1.0
species: 883848

173065
type: SpeciesReference
stoichiometry: 1.0
species: 883768

173053
type: SpeciesReference
stoichiometry: 1.0
species: 883328

885308
type: Reaction
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

172023
type: KineticLaw
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

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

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

172011
type: SpeciesReference
stoichiometry: 1.0
species: 883548

171999
type: SpeciesReference
stoichiometry: 1.0
species: 883508

171986
type: SpeciesReference
stoichiometry: 1.0
species: 883428

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

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

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

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

172981
type: SpeciesReference
stoichiometry: 1.0
species: 883828

172969
type: SpeciesReference
stoichiometry: 1.0
species: 883768

172957
type: SpeciesReference
stoichiometry: 1.0
species: 883428

884588
type: Reaction
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

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

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

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

170404
type: SpeciesReference
stoichiometry: 1.0
species: 883108

170392
type: SpeciesReference
stoichiometry: 1.0
species: 884268

170380
type: SpeciesReference
stoichiometry: 1.0
species: 883148

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

884568
type: Reaction
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

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

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

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

170356
type: SpeciesReference
stoichiometry: 1.0
species: 883068

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

170344
type: SpeciesReference
stoichiometry: 1.0
species: 883148

170332
type: SpeciesReference
stoichiometry: 1.0
species: 883168

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

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

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

171962
type: SpeciesReference
stoichiometry: 1.0
species: 883508

171950
type: SpeciesReference
stoichiometry: 1.0
species: 883428

171938
type: SpeciesReference
stoichiometry: 1.0
species: 883528

885268
type: Reaction
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

171926
type: KineticLaw
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

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

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

171914
type: SpeciesReference
stoichiometry: 1.0
species: 883528

171901
type: SpeciesReference
stoichiometry: 1.0
species: 883508

171889
type: SpeciesReference
stoichiometry: 1.0
species: 883288

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

171877
type: KineticLaw
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

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

171865
type: SpeciesReference
stoichiometry: 1.0
species: 883448

171853
type: SpeciesReference
stoichiometry: 1.0
species: 883368

171841
type: SpeciesReference
stoichiometry: 1.0
species: 883488

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

885228
type: Reaction
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

171829
type: KineticLaw
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

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

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

171817
type: SpeciesReference
stoichiometry: 1.0
species: 883488

171805
type: SpeciesReference
stoichiometry: 1.0
species: 883448

171793
type: SpeciesReference
stoichiometry: 1.0
species: 883428

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

171637
type: KineticLaw
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

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

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

171625
type: SpeciesReference
stoichiometry: 1.0
species: 883408

171613
type: SpeciesReference
stoichiometry: 1.0
species: 883368

171600
type: SpeciesReference
stoichiometry: 1.0
species: 883348

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

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

172933
type: SpeciesReference
stoichiometry: 1.0
species: 883768

172921
type: SpeciesReference
stoichiometry: 1.0
species: 883428

172909
type: SpeciesReference
stoichiometry: 1.0
species: 883808

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

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

885108
type: Reaction
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

171540
type: KineticLaw
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

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

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

171527
type: SpeciesReference
stoichiometry: 1.0
species: 883388

171514
type: SpeciesReference
stoichiometry: 1.0
species: 883368

171501
type: SpeciesReference
stoichiometry: 1.0
species: 883308

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

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

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

172640
type: SpeciesReference
stoichiometry: 1.0
species: 883648

172628
type: SpeciesReference
stoichiometry: 1.0
species: 883588

172616
type: SpeciesReference
stoichiometry: 1.0
species: 883728

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

885548
type: Reaction
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

172604
type: KineticLaw
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

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

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

172592
type: SpeciesReference
stoichiometry: 1.0
species: 883728

172580
type: SpeciesReference
stoichiometry: 1.0
species: 883648

172568
type: SpeciesReference
stoichiometry: 1.0
species: 883568

884708
type: Reaction
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

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

195691
type: LocalParameter
units: 169930
value: 0.0

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

170635
type: SpeciesReference
stoichiometry: 1.0
species: 883748

170623
type: SpeciesReference
stoichiometry: 1.0
species: 883568

885508
type: Reaction
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

172507
type: KineticLaw
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

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

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

172495
type: SpeciesReference
stoichiometry: 1.0
species: 883708

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

172483
type: SpeciesReference
stoichiometry: 1.0
species: 883648

172470
type: SpeciesReference
stoichiometry: 1.0
species: 883748

884988
type: Reaction
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

171241
type: KineticLaw
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

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

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

171229
type: SpeciesReference
stoichiometry: 1.0
species: 883188

171217
type: SpeciesReference
stoichiometry: 1.0
species: 884388

171205
type: SpeciesReference
stoichiometry: 1.0
species: 883248

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

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

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

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

195788
type: LocalParameter
units: 169894
value: 0.0666666666666667

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

172727
type: SpeciesReference
stoichiometry: 1.0
species: 883348

172714
type: SpeciesReference
stoichiometry: 1.0
species: 883648

885028
type: Reaction
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

171340
type: KineticLaw
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

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

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

171328
type: SpeciesReference
stoichiometry: 1.0
species: 883208

171315
type: SpeciesReference
stoichiometry: 1.0
species: 884388

171302
type: SpeciesReference
stoichiometry: 1.0
species: 884228

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

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

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

171278
type: SpeciesReference
stoichiometry: 1.0
species: 884388

171265
type: SpeciesReference
stoichiometry: 1.0
species: 883268

171253
type: SpeciesReference
stoichiometry: 1.0
species: 883188

884888
type: Reaction
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

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

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

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

171034
type: SpeciesReference
stoichiometry: 1.0
species: 884048

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

171021
type: SpeciesReference
stoichiometry: 1.0
species: 884288

171009
type: SpeciesReference
stoichiometry: 1.0
species: 884088

884868
type: Reaction
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

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

195709
type: LocalParameter
units: 169930
value: 0.0

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

170985
type: SpeciesReference
stoichiometry: 1.0
species: 884348

170973
type: SpeciesReference
stoichiometry: 1.0
species: 883168

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

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

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

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

172252
type: SpeciesReference
stoichiometry: 1.0
species: 883608

172239
type: SpeciesReference
stoichiometry: 1.0
species: 883748

172227
type: SpeciesReference
stoichiometry: 1.0
species: 883628

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

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

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

173610
type: SpeciesReference
stoichiometry: 1.0
species: 884048

173598
type: SpeciesReference
stoichiometry: 1.0
species: 883168

173586
type: SpeciesReference
stoichiometry: 1.0
species: 884068

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

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

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

173706
type: SpeciesReference
stoichiometry: 1.0
species: 884128

173694
type: SpeciesReference
stoichiometry: 1.0
species: 884168

173682
type: SpeciesReference
stoichiometry: 1.0
species: 884148

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

884488
type: Reaction
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

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

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

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

170183
type: SpeciesReference
stoichiometry: 1.0
species: 883028

170171
type: SpeciesReference
stoichiometry: 1.0
species: 883088

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

171781
type: KineticLaw
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

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

171769
type: SpeciesReference
stoichiometry: 1.0
species: 883448

171757
type: SpeciesReference
stoichiometry: 1.0
species: 883428

171745
type: SpeciesReference
stoichiometry: 1.0
species: 883468

885668
type: Reaction
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

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

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

172884
type: SpeciesReference
stoichiometry: 1.0
species: 883808

172872
type: SpeciesReference
stoichiometry: 1.0
species: 883768

172860
type: SpeciesReference
stoichiometry: 1.0
species: 883368

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

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

172836
type: SpeciesReference
stoichiometry: 1.0
species: 883768

172824
type: SpeciesReference
stoichiometry: 1.0
species: 883248

172812
type: SpeciesReference
stoichiometry: 1.0
species: 883788

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

885388
type: Reaction
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

172215
type: KineticLaw
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

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

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

172203
type: SpeciesReference
stoichiometry: 1.0
species: 883628

172191
type: SpeciesReference
stoichiometry: 1.0
species: 883608

172179
type: SpeciesReference
stoichiometry: 1.0
species: 884308

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

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

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

171475
type: SpeciesReference
stoichiometry: 1.0
species: 884388

171463
type: SpeciesReference
stoichiometry: 1.0
species: 884128

171450
type: SpeciesReference
stoichiometry: 1.0
species: 883228

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

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

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

172544
type: SpeciesReference
stoichiometry: 1.0
species: 883648

172532
type: SpeciesReference
stoichiometry: 1.0
species: 883568

172519
type: SpeciesReference
stoichiometry: 1.0
species: 883708

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

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

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

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

170271
type: SpeciesReference
stoichiometry: 1.0
species: 882968

170258
type: SpeciesReference
stoichiometry: 1.0
species: 883128

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

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

173670
type: KineticLaw
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

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

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

173658
type: SpeciesReference
stoichiometry: 1.0
species: 884148

173646
type: SpeciesReference
stoichiometry: 1.0
species: 884128

173634
type: SpeciesReference
stoichiometry: 1.0
species: 884188

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

885948
type: Reaction
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

173574
type: KineticLaw
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

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

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

173562
type: SpeciesReference
stoichiometry: 1.0
species: 884068

173550
type: SpeciesReference
stoichiometry: 1.0
species: 884048

173538
type: SpeciesReference
stoichiometry: 1.0
species: 884348

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

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

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

173514
type: SpeciesReference
stoichiometry: 1.0
species: 884008

173502
type: SpeciesReference
stoichiometry: 1.0
species: 883168

173490
type: SpeciesReference
stoichiometry: 1.0
species: 884028

884668
type: Reaction
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

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

195687
type: LocalParameter
units: 169930
value: 0.0

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

170562
type: SpeciesReference
stoichiometry: 1.0
species: 884328

170550
type: SpeciesReference
stoichiometry: 1.0
species: 883588

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

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

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

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

170147
type: SpeciesReference
stoichiometry: 1.0
species: 883008

170135
type: SpeciesReference
stoichiometry: 1.0
species: 882948

884448
type: Reaction
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

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

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

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

170111
type: SpeciesReference
stoichiometry: 1.0
species: 883088

170099
type: SpeciesReference
stoichiometry: 1.0
species: 882948

170087
type: SpeciesReference
stoichiometry: 1.0
species: 884268

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

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

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

172445
type: SpeciesReference
stoichiometry: 1.0
species: 883648

172433
type: SpeciesReference
stoichiometry: 1.0
species: 884088

172421
type: SpeciesReference
stoichiometry: 1.0
species: 883688

885468
type: Reaction
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

172409
type: KineticLaw
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

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

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

172397
type: SpeciesReference
stoichiometry: 1.0
species: 883688

172385
type: SpeciesReference
stoichiometry: 1.0
species: 883648

172373
type: SpeciesReference
stoichiometry: 1.0
species: 883868

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

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

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

172788
type: SpeciesReference
stoichiometry: 1.0
species: 883788

172776
type: SpeciesReference
stoichiometry: 1.0
species: 883768

172764
type: SpeciesReference
stoichiometry: 1.0
species: 883268

884548
type: Reaction
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

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

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

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

170307
type: SpeciesReference
stoichiometry: 1.0
species: 883048

170295
type: SpeciesReference
stoichiometry: 1.0
species: 883148

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

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

195764
type: LocalParameter
units: 169894
value: 0.0666666666666667

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

172143
type: SpeciesReference
stoichiometry: 1.0
species: 883348

172131
type: SpeciesReference
stoichiometry: 1.0
species: 883648

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

172119
type: KineticLaw
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)

195762
type: LocalParameter
units: 169894
value: 0.0666666666666667

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

172095
type: SpeciesReference
stoichiometry: 1.0
species: 883308

172083
type: SpeciesReference
stoichiometry: 1.0
species: 883348

884508
type: Reaction
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

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

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

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

170233
type: SpeciesReference
stoichiometry: 1.0
species: 882988

170220
type: SpeciesReference
stoichiometry: 1.0
species: 883168

170207
type: SpeciesReference
stoichiometry: 1.0
species: 882948

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

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

195721
type: LocalParameter
units: 169930
value: 0.0

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

171180
type: SpeciesReference
stoichiometry: 1.0
species: 884228

171168
type: SpeciesReference
stoichiometry: 1.0
species: 884208

884948
type: Reaction
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

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

195718
type: LocalParameter
units: 169930
value: 0.0

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

171144
type: SpeciesReference
stoichiometry: 1.0
species: 884188

171132
type: SpeciesReference
stoichiometry: 1.0
species: 884168

884848
type: Reaction
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

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

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

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

170949
type: SpeciesReference
stoichiometry: 1.0
species: 884008

170937
type: SpeciesReference
stoichiometry: 1.0
species: 883888

170925
type: SpeciesReference
stoichiometry: 1.0
species: 884268

885868
type: Reaction
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

173380
type: KineticLaw
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

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

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

173367
type: SpeciesReference
stoichiometry: 1.0
species: 883988

173355
type: SpeciesReference
stoichiometry: 1.0
species: 883968

173343
type: SpeciesReference
stoichiometry: 1.0
species: 884348

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

170913
type: KineticLaw
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_

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

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

170901
type: SpeciesReference
stoichiometry: 1.0
species: 883968

170889
type: SpeciesReference
stoichiometry: 1.0
species: 883888

170877
type: SpeciesReference
stoichiometry: 1.0
species: 884368

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

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

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

173319
type: SpeciesReference
stoichiometry: 1.0
species: 883928

173307
type: SpeciesReference
stoichiometry: 1.0
species: 883168

173294
type: SpeciesReference
stoichiometry: 1.0
species: 883948