begin name
neves1
end name

begin reactions
A1 {1.0}c2R2C2cyto + {1.0}cAMPcyto = {1.0}c3R2C2cyto
A2 {1.0}c3R2C2cyto + {1.0}cAMPcyto = {1.0}PKAcyto
ACactivation {1.0}Gascyto + {1.0}ACcytomem = {1.0}ACactivecytomem
ACactive {1.0}ATPcyto = {1.0}cAMPcyto
ACbasal {1.0}ATPcyto = {1.0}cAMPcyto
B1 {1.0}R2C2cyto + {1.0}cAMPcyto = {1.0}cR2C2cyto
B2 {1.0}cR2C2cyto + {1.0}cAMPcyto = {1.0}c2R2C2cyto
GRK {1.0}isoBARcytomem = {1.0}isoBARpcytomem
GRKbg {1.0}isoBARcytomem = {1.0}isoBARpcytomem
GTPase {1.0}Gascyto = {1.0}GGDPcyto
GbindsBAR {1.0}BARcytomem + {1.0}Gproteincyto = {1.0}BARGcytomem
GbindsisoBAR {1.0}isoBARcytomem + {1.0}Gproteincyto = {1.0}isoBARGcytomem
MEKactivatesMAPK {1.0}MAPKcyto = {1.0}MAPKactivecyto
PDE4 {1.0}cAMPcyto = {1.0}AMPcyto
PKAPPDE {1.0}PDE4cyto = {1.0}PDE4Pcyto
PKAPPTP {1.0}PTPcyto = {1.0}PTPPKAcyto
PKAactivatesRaf {1.0}BRafcyto = {1.0}BRafactivecyto
PPaseMAPK {1.0}MAPKactivecyto = {1.0}MAPKcyto
PPaseRaf {1.0}BRafactivecyto = {1.0}BRafcyto
PPasemek {1.0}MEKactivecyto = {1.0}MEKcyto
PTP {1.0}MAPKactivecyto = {1.0}MAPKcyto
PTPPKA {1.0}MAPKactivecyto = {1.0}MAPKcyto
RafactivatesMEK {1.0}MEKcyto = {1.0}MEKactivecyto
activateGs {1.0}isoBARGcytomem = {1.0}isoBARcytomem + {1.0}bgcyto + {1.0}Gascyto
bgbindsGRK {1.0}GRKcyto + {1.0}bgcyto = {1.0}GRKbgcyto
highKMPDE {1.0}cAMPcyto = {1.0}AMPcyto
isobindsBAR {1.0}BARcytomem + {1.0}isoextra = {1.0}isoBARcytomem
isobindsBARg {1.0}isoextra + {1.0}BARGcytomem = {1.0}isoBARGcytomem
pde4p {1.0}cAMPcyto = {1.0}AMPcyto
pp2a4 {1.0}PDE4Pcyto = {1.0}PDE4cyto
ppptp {1.0}PTPPKAcyto = {1.0}PTPcyto
trimer {1.0}bgcyto + {1.0}GGDPcyto = {1.0}Gproteincyto
end reactions

begin rate equations
A1 = (cyto*(-0.00166112956810631*A1Kr*c3R2C2cyto[t] + 2.7593514420370556*^-6*A1Kf*c2R2C2cyto[t]*cAMPcyto[t]))/KMOLE
A2 = (cyto*(2.7593514420370556*^-6*A2Kf*c3R2C2cyto[t]*cAMPcyto[t] - 0.00166112956810631*A2Kr*PKAcyto[t]))/KMOLE
ACactivation = cytomem*(-(ACactivationKrACactivation*ACactivecytomem[t]) + 0.00166112956810631*ACactivationKfACactivation*ACcytomem[t]*Gascyto[t])
ACactive = (0.00166112956810631*cytomem*VmaxACactiveACactive*ATPcyto[t])/(ACactiveKmACactive + 0.00166112956810631*ATPcyto[t])
ACbasal = (0.00166112956810631*cytomem*VmaxACbasalACbasal*ATPcyto[t])/(ACbasalKmACbasal + 0.00166112956810631*ATPcyto[t])
B1 = (cyto*(-0.00166112956810631*B1Kr*cR2C2cyto[t] + 2.7593514420370556*^-6*B1Kf*cAMPcyto[t]*R2C2cyto[t]))/KMOLE
B2 = (cyto*(-0.00166112956810631*B2Kr*c2R2C2cyto[t] + 2.7593514420370556*^-6*B2Kf*cAMPcyto[t]*cR2C2cyto[t]))/KMOLE
GRK = (cytomem*VmaxgrkGRK*isoBARcytomem[t])/(GRKKmgrk + isoBARcytomem[t])
GRKbg = (cytomem*VmaxGRKbgGRKbg*isoBARcytomem[t])/(GRKbgKmGRKbg + isoBARcytomem[t])
GTPase = (cyto*(0.00166112956810631*GTPaseKfGTPase*Gascyto[t] - 0.00166112956810631*GTPaseKrGTPase*GGDPcyto[t]))/KMOLE
GbindsBAR = cytomem*(-(GbindsBARKrGbindsBAR*BARGcytomem[t]) + 0.00166112956810631*GbindsBARKfGbindsBAR*BARcytomem[t]*Gproteincyto[t])
GbindsisoBAR = cytomem*(0.00166112956810631*GbindsisoBARKfGbindsisoBAR*Gproteincyto[t]*isoBARcytomem[t] - GbindsisoBARKrGbindsisoBAR*isoBARGcytomem[t])
MEKactivatesMAPK = (0.00166112956810631*cyto*VmaxMEKactivatesMAPK*MAPKcyto[t])/(KMOLE*(MEKactivatesMAPKKm + 0.00166112956810631*MAPKcyto[t]))
PDE4 = (0.00166112956810631*cyto*VmaxPDE4PDE4*cAMPcyto[t])/(KMOLE*(PDE4KmPDE4 + 0.00166112956810631*cAMPcyto[t]))
PKAPPDE = (0.00166112956810631*cyto*VmaxPKAPPDE*PDE4cyto[t])/(KMOLE*(PKAPPDEKm + 0.00166112956810631*PDE4cyto[t]))
PKAPPTP = (0.00166112956810631*cyto*VmaxPKAPPTP*PTPcyto[t])/(KMOLE*(PKAPPTPKm + 0.00166112956810631*PTPcyto[t]))
PKAactivatesRaf = (0.00166112956810631*cyto*VmaxPKAactivatesRaf*BRafcyto[t])/(KMOLE*(PKAactivatesRafKm + 0.00166112956810631*BRafcyto[t]))
PPaseMAPK = (0.00166112956810631*cyto*VmaxPPaseMAPK*MAPKactivecyto[t])/(KMOLE*(PPaseMAPKKm + 0.00166112956810631*MAPKactivecyto[t]))
PPaseRaf = (0.00166112956810631*cyto*VmaxPPaseRaf*BRafactivecyto[t])/(KMOLE*(PPaseRafKm + 0.00166112956810631*BRafactivecyto[t]))
PPasemek = (0.00166112956810631*cyto*VmaxPPasemek*MEKactivecyto[t])/(KMOLE*(PPasemekKm + 0.00166112956810631*MEKactivecyto[t]))
PTP = (0.00166112956810631*cyto*VmaxPTP*MAPKactivecyto[t])/(KMOLE*(PTPKm + 0.00166112956810631*MAPKactivecyto[t]))
PTPPKA = (0.00166112956810631*cyto*VmaxPTPPKA*MAPKactivecyto[t])/(KMOLE*(PTPPKAKm + 0.00166112956810631*MAPKactivecyto[t]))
RafactivatesMEK = (0.00166112956810631*cyto*VmaxRafactivatesMEK*MEKcyto[t])/(KMOLE*(RafactivatesMEKKm + 0.00166112956810631*MEKcyto[t]))
activateGs = cytomem*(-2.7593514420370556*^-6*activateGsKractivateGs*bgcyto[t]*Gascyto[t]*isoBARcytomem[t] + activateGsKfactivateGs*isoBARGcytomem[t])
bgbindsGRK = (cyto*(-0.00166112956810631*bgbindsGRKKrbgbindsGRK*GRKbgcyto[t] + 2.7593514420370556*^-6*bgbindsGRKKfbgbindsGRK*bgcyto[t]*GRKcyto[t]))/KMOLE
highKMPDE = (0.00166112956810631*cyto*VmaxhighKMPDE*cAMPcyto[t])/(KMOLE*(highKMPDEKm + 0.00166112956810631*cAMPcyto[t]))
isobindsBAR = cytomem*(-(isobindsBARKr*isoBARcytomem[t]) + 0.00166112956810631*isobindsBARKf*BARcytomem[t]*isoextra[t])
isobindsBARg = cytomem*(-(isobindsBARgKr*isoBARGcytomem[t]) + 0.00166112956810631*isobindsBARgKf*BARGcytomem[t]*isoextra[t])
pde4p = (0.00166112956810631*cyto*Vmaxpde4ppde4p*cAMPcyto[t])/(KMOLE*(pde4pKmpde4p + 0.00166112956810631*cAMPcyto[t]))
pp2a4 = (0.00166112956810631*cyto*Vmaxpp2a4pp2a4*PDE4Pcyto[t])/(KMOLE*(pp2a4Kmpp2a4 + 0.00166112956810631*PDE4Pcyto[t]))
ppptp = (0.00166112956810631*cyto*Vmaxppptp*PTPPKAcyto[t])/(KMOLE*(ppptpKm + 0.00166112956810631*PTPPKAcyto[t]))
trimer = (cyto*(2.7593514420370556*^-6*trimerKftrimer*bgcyto[t]*GGDPcyto[t] - 0.00166112956810631*trimerKrtrimer*Gproteincyto[t]))/KMOLE
end rate equations

begin parameters
KMOLE = 0.00166112956810631
kcatPKAPPTP = 0.2
kcatPKAactivatesRaf = 10.0
kcatPPaseMAPK = 0.636
kcatPPaseRaf = 5.0
kcatPPasemek = 5.0
kcatPTP = 1.06
kcatPTPPKA = 0.1
kcatppptpppptp = 5.0
activateGsI = 0.0
activateGsKfactivateGs = 0.025
activateGsKractivateGs = 0.0
pde4pKmpde4p = 1.3
PPaseRafKm = 15.7
isobindsBARI = 0.0
isobindsBARKf = 1.0
isobindsBARKr = 0.2
PDE4KmPDE4 = 1.3
bgbindsGRKKfbgbindsGRK = 1.0
bgbindsGRKKrbgbindsGRK = 0.25
MEKactivatesMAPKKm = 0.046296
PKAactivatesRafKm = 0.5
ACactiveI = 0.0
ACactiveKmACactive = 32.0
GTPaseKfGTPase = 0.06667
GTPaseKrGTPase = 0.0
trimerKftrimer = 6.0
trimerKrtrimer = 0.0
GbindsisoBARI = 0.0
GbindsisoBARKfGbindsisoBAR = 10.0
GbindsisoBARKrGbindsisoBAR = 0.1
A2Kf = 8.35
A2Kr = 0.0167
highKMPDEKm = 15.0
PKAPPTPKm = 0.1
ACactivationI = 0.0
ACactivationKfACactivation = 500.0
ACactivationKrACactivation = 1.0
ACbasalI = 0.0
ACbasalKmACbasal = 1030.0
B1Kf = 0.0059
B1Kr = 0.00028
GRKI = 0.0
GRKKmgrk = 15.0
PKAPPDEKm = 0.5
RafactivatesMEKKm = 0.15909
PTPPKAKm = 9.0
B2Kf = 0.0059
B2Kr = 0.00028
PTPKm = 0.46
isobindsBARgI = 0.0
isobindsBARgKf = 1.0
isobindsBARgKr = 0.062
PPaseMAPKKm = 0.77
pp2a4Kmpp2a4 = 8.0
ppptpKm = 6.0
GRKbgI = 0.0
GRKbgKmGRKbg = 4.0
GbindsBARI = 0.0
GbindsBARKfGbindsBAR = 0.3
GbindsBARKrGbindsBAR = 0.1
PPasemekKm = 15.7
A1Kf = 8.35
A1Kr = 0.0167
cyto = 1.0
cytomem = 0.2
extra = 0.111111111111111
end parameters

begin initial conditions
ACPKAcytomem[0] = ACPKAcytomemi
ACactivecytomem[0] = ACactivecytomemi
ACcytomem[0] = ACcytomemi
AMPcyto[0] = AMPcytoi
ATPcyto[0] = ATPcytoi
BARGcytomem[0] = BARGcytomemi
BARcytomem[0] = BARcytomemi
BRafactivecyto[0] = BRafactivecytoi
BRafcyto[0] = BRafcytoi
GRKbgcyto[0] = GRKbgcytoi
GRKcyto[0] = GRKcytoi
GGDPcyto[0] = GGDPcytoi
Gascyto[0] = Gascytoi
Gproteincyto[0] = Gproteincytoi
MAPKactivecyto[0] = MAPKactivecytoi
MAPKcyto[0] = MAPKcytoi
MEKactivecyto[0] = MEKactivecytoi
MEKcyto[0] = MEKcytoi
PDE4Pcyto[0] = PDE4Pcytoi
PDE4cyto[0] = PDE4cytoi
PDEhighkmcyto[0] = PDEhighkmcytoi
PKAcyto[0] = PKAcytoi
PP2Acyto[0] = PP2Acytoi
PPPDEcyto[0] = PPPDEcytoi
PTPPKAcyto[0] = PTPPKAcytoi
PTPPPcyto[0] = PTPPPcytoi
PTPcyto[0] = PTPcytoi
R2C2cyto[0] = R2C2cytoi
bgcyto[0] = bgcytoi
c2R2C2cyto[0] = c2R2C2cytoi
c3R2C2cyto[0] = c3R2C2cytoi
cAMPcyto[0] = cAMPcytoi
cR2C2cyto[0] = cR2C2cytoi
isoBARGcytomem[0] = isoBARGcytomemi
isoBARcytomem[0] = isoBARcytomemi
isoBARpcytomem[0] = isoBARpcytomemi
isoextra[0] = isoextrai
end initial conditions

begin initial values
ACPKAcytomemi = 0.0
ACactivecytomemi = 0.0
ACcytomemi = 300.0
AMPcytoi = 3010000.0
ATPcytoi = 3010000.0
BARGcytomemi = 0.0
BARcytomemi = 94.0
BRafactivecytoi = 0.0
BRafcytoi = 120.4
GRKbgcytoi = 0.0
GRKcytoi = 0.602
GGDPcytoi = 0.0
Gascytoi = 0.0
Gproteincytoi = 2167.2
MAPKactivecytoi = 0.0
MAPKcytoi = 216.72
MEKactivecytoi = 0.0
MEKcytoi = 108.36
PDE4Pcytoi = 0.0
PDE4cytoi = 240.8
PDEhighkmcytoi = 301.0
PKAcytoi = 0.0
PP2Acytoi = 60.2
PPPDEcytoi = 120.4
PTPPKAcytoi = 0.0
PTPPPcytoi = 60.2
PTPcytoi = 120.4
R2C2cytoi = 120.4
bgcytoi = 0.0
c2R2C2cytoi = 0.0
c3R2C2cytoi = 0.0
cAMPcytoi = 0.0
cR2C2cytoi = 0.0
isoBARGcytomemi = 0.0
isoBARcytomemi = 0.0
isoBARpcytomemi = 0.0
isoextrai = 6020.0
end initial values

begin assignment rules
Vmaxpde4ppde4p := 0.0332225913621262*PDE4Pcyto[t]
VmaxPPasemek := 0.00166112956810631*kcatPPasemek*PP2Acyto[t]
VmaxGRKbgGRKbg := 0.0022259136212624555*GRKbgcyto[t]
Vmaxppptp := 0.00166112956810631*kcatppptpppptp*PTPPPcyto[t]
Vmaxpp2a4pp2a4 := 0.00830564784053155*PPPDEcyto[t]
VmaxPPaseMAPK := 0.00166112956810631*kcatPPaseMAPK*PP2Acyto[t]
VmaxPTP := 0.00166112956810631*kcatPTP*PTPcyto[t]
VmaxPTPPKA := 0.00166112956810631*kcatPTPPKA*PTPPKAcyto[t]
VmaxRafactivatesMEK := 0.00017441860465116255*BRafactivecyto[t]
VmaxPKAPPDE := 0.0166112956810631*PKAcyto[t]
VmaxgrkGRK := 0.00017275747508305623*GRKcyto[t]
VmaxACbasalACbasal := 0.2*ACcytomem[t]
VmaxPKAPPTP := 0.00166112956810631*kcatPKAPPTP*PKAcyto[t]
VmaxhighKMPDE := 0.01328903654485048*PDEhighkmcyto[t]
VmaxACactiveACactive := 8.5*ACactivecytomem[t]
VmaxPKAactivatesRaf := 0.00166112956810631*kcatPKAactivatesRaf*PKAcyto[t]
VmaxMEKactivatesMAPK := 0.0002491694352159465*MEKactivecyto[t]
VmaxPDE4PDE4 := 0.01328903654485048*PDE4cyto[t]
VmaxPPaseRaf := 0.00166112956810631*kcatPPaseRaf*PP2Acyto[t]
end assignment rules

begin function definitions
end function definitions

begin events
end events

begin process annotations
end process annotations

begin species annotations
AMP_cyto http://identifiers.org/chebi/CHEBI:16027
AMP_cyto http://identifiers.org/kegg.compound/C00020
ATP_cyto http://identifiers.org/chebi/CHEBI:15422
ATP_cyto http://identifiers.org/kegg.compound/C00002
G_protein_cyto http://identifiers.org/go/GO:0005834
cAMP_cyto http://identifiers.org/chebi/CHEBI:17489
cAMP_cyto http://identifiers.org/kegg.compound/C00575
end species annotations

begin units
end units