begin parameters Lig_tot 6.0e3 Rec_tot 4.0e2 Lyn_tot 2.8e1 Syk_tot 4.0e2 kp1 1.328452377888242e-7 km1 0 kp2 2.5e-1 km2 0 kpL 5e-2 kmL 20 kpLs 5e-2 kmLs 0.12 kpS 6e-2 kmS 0.13 kpSs 6e-2 kmSs 0.13 pLb 30 pLbs 100 pLg 1 pLgs 3 pLS 30 pLSs 100 pSS 100 pSSs 200 dm 20 dc 20 end parameters begin species Lig(l,l) Lig_tot Lyn(U,SH2) Lyn_tot Syk(tSH2,l~Y,a~Y) Syk_tot Rec(a,b~Y,g~Y) Rec_tot end species begin reaction_rules # Ligand-receptor binding 1 Rec(a) + Lig(l,l) <-> Rec(a!1).Lig(l!1,l) kp1, km1 # Receptor-aggregation 2 Rec(a) + Lig(l,l!1) <-> Rec(a!2).Lig(l!2,l!1) kp2,km2 # Constitutive Lyn-receptor binding 3 Rec(b~Y) + Lyn(U,SH2) <-> Rec(b~Y!1).Lyn(U!1,SH2) kpL, kmL # Transphosphorylation of beta by constitutive Lyn 4 Lig(l!1,l!2).Lyn(U!3,SH2).Rec(a!2,b~Y!3).Rec(a!1,b~Y) -> Lig(l!1,l!2).Lyn(U!3,SH2).Rec(a!2,b~Y!3).Rec(a!1,b~pY) pLb # Transphosphorylation of gamma by constitutive Lyn 5 Lig(l!1,l!2).Lyn(U!3,SH2).Rec(a!2,b~Y!3).Rec(a!1,g~Y) -> Lig(l!1,l!2).Lyn(U!3,SH2).Rec(a!2,b~Y!3).Rec(a!1,g~pY) pLg # Lyn-receptor binding through SH2 domain 6 Rec(b~pY) + Lyn(U,SH2) <-> Rec(b~pY!1).Lyn(U,SH2!1) kpLs, kmLs # Transphosphorylation of beta by SH2-bound Lyn 7 Lig(l!1,l!2).Lyn(U,SH2!3).Rec(a!2,b~pY!3).Rec(a!1,b~Y) -> Lig(l!1,l!2).Lyn(U,SH2!3).Rec(a!2,b~pY!3).Rec(a!1,b~pY) pLbs # Transphosphorylation of gamma by SH2-bound Lyn 8 Lig(l!1,l!2).Lyn(U,SH2!3).Rec(a!2,b~pY!3).Rec(a!1,g~Y) -> Lig(l!1,l!2).Lyn(U,SH2!3).Rec(a!2,b~pY!3).Rec(a!1,g~pY) pLgs # Syk-receptor binding through tSH2 domain 9 Rec(g~pY) + Syk(tSH2) <-> Rec(g~pY!1).Syk(tSH2!1) kpS, kmS # Transphosphorylation of Syk by constitutive Lyn 10 Lig(l!1,l!2).Lyn(U!3,SH2).Rec(a!2,b~Y!3).Rec(a!1,g~pY!4).Syk(tSH2!4,l~Y) -> \ Lig(l!1,l!2).Lyn(U!3,SH2).Rec(a!2,b~Y!3).Rec(a!1,g~pY!4).Syk(tSH2!4,l~pY) pLS # Transphosphorylation of Syk by SH2-bound Lyn 11 Lig(l!1,l!2).Lyn(U,SH2!3).Rec(a!2,b~pY!3).Rec(a!1,g~pY!4).Syk(tSH2!4,l~Y) -> \ Lig(l!1,l!2).Lyn(U,SH2!3).Rec(a!2,b~pY!3).Rec(a!1,g~pY!4).Syk(tSH2!4,l~pY) pLSs # Transphosphorylation of Syk by Syk not phosphorylated on aloop 12 Lig(l!1,l!2).Syk(tSH2!3,a~Y).Rec(a!2,g~pY!3).Rec(a!1,g~pY!4).Syk(tSH2!4,a~Y) -> \ Lig(l!1,l!2).Syk(tSH2!3,a~Y).Rec(a!2,g~pY!3).Rec(a!1,g~pY!4).Syk(tSH2!4,a~pY) pSS # Transphosphorylation of Syk by Syk phosphorylated on aloop 13 Lig(l!1,l!2).Syk(tSH2!3,a~pY).Rec(a!2,g~pY!3).Rec(a!1,g~pY!4).Syk(tSH2!4,a~Y) -> \ Lig(l!1,l!2).Syk(tSH2!3,a~pY).Rec(a!2,g~pY!3).Rec(a!1,g~pY!4).Syk(tSH2!4,a~pY) pSSs # Dephosphorylation of Rec beta 14 Rec(b~pY)-> Rec(b~Y) dm # Dephosphorylation of Rec gamma 15 Rec(g~pY)-> Rec(g~Y) dm # Dephosphorylation of Syk at membrane 16 Syk(tSH2!1,l~pY)-> Syk(tSH2!1,l~Y) dm 17 Syk(tSH2!1,a~pY)-> Syk(tSH2!1,a~Y) dm # Dephosphorylation of Syk in cytosol 18 Syk(tSH2,l~pY)-> Syk(tSH2,l~Y) dc 19 Syk(tSH2,a~pY)-> Syk(tSH2,a~Y) dc end reaction_rules begin observables Molecules LynFree Lyn(U,SH2) Molecules RecMon Rec(a) Rec(a!1).Lig(l!1,l) Molecules RecDim Rec.Rec #Molecules RecPbeta Rec(b~pY) Rec(b~pY!1) Molecules RecPbeta Rec(b~pY!?) Molecules RecPgamma Rec(g~pY) Rec(g~pY!1) Molecules RecSyk Rec(g~pY!1).Syk(tSH2!1) Molecules RecSykPS Rec(g~pY!1).Syk(tSH2!1,a~pY) Molecules SykTest Syk Molecules LynTest Lyn Molecules RecTest Rec end observables generate_network({overwrite=>1}); simulate_ode({t_end=>600,n_steps=>10,atol=>1e-8,rtol=>1e-8}); writeSBML({});