%var: 'Lig_tot' 6.0e3 %var: 'Rec_tot' 4.0e2 %var: 'Lyn_tot' 2.8e1 %var: 'Fyn_tot' 4.0e2 %var: 'Syk_tot' 4.0e2 %var: 'kp1' 1.32845238e-7 %var: 'km1' 0 %var: 'kp2' 2.5e-1 %var: 'km2' 0 %var: 'kpL' 5e-2 %var: 'kmL' 20 %var: 'kpLs' 5e-2 %var: 'kmLs' 0.12 %var: 'kpF' 5e-2 %var: 'kmF' 20 %var: 'kpS' 6e-2 %var: 'kmS' 0.13 %var: 'kpSs' 6e-2 %var: 'kmSs' 0.13 %var: 'pLb' 30 %var: 'pLbs' 100 %var: 'pLg' 1 %var: 'pLgs' 3 %var: 'pLS' 30 %var: 'pLSs' 100 %var: 'pSS' 100 %var: 'pSSs' 200 %var: 'pLF' 30 %var: 'pLFs' 100 %var: 'dm' 20 %var: 'dc' 20 %var: 'klig' 1 %init: 'Lig_tot' Lig(l1,l2,a~1) %init: 'Lyn_tot' Lyn(U,SH2,a~Y) %init: 'Fyn_tot' Fyn(SH2,a~Y,t~Y) %init: 'Syk_tot' Syk(tSH2,l~Y,a~Y) %init: 'Rec_tot' Rec(a,b~Y,g~Y) %agent: Lig(l1,l2,a~1~2) %agent: Lyn(U,SH2,a~Y~pY) %agent: Fyn(SH2,a~Y~pY,t~Y) %agent: Syk(tSH2,l~Y~pY,a~Y~pY) %agent: Rec(a,b~Y~pY,g~Y~pY) # Ligand flips state so there are two ligand types Lig(a~1) <-> Lig(a~2) @'klig','klig' # Ligand-receptor binding Rec(a), Lig(l1,l2) <-> Rec(a!1),Lig(l1!1,l2) @'kp1', 'km1' Rec(a), Lig(l2,l1) <-> Rec(a!1),Lig(l2!1,l1) @'kp1', 'km1' # Receptor-aggregation Rec(a), Lig(l1,l2!_) <-> Rec(a!2), Lig(l1!2,l2!_) @'kp2','km2' Rec(a), Lig(l2,l1!_) <-> Rec(a!2), Lig(l2!2,l1!_) @'kp2','km2' # Constitutive Lyn-receptor binding Rec(b~Y), Lyn(U,SH2) <-> Rec(b~Y!1), Lyn(U!1,SH2) @'kpL', 'kmL' # Transphosphorylation of beta by constitutive Lyn Lig(l1!1,l2!2), Lyn(U!3,SH2), Rec(a!2,b~Y!3), Rec(a!1,b~Y) -> Lig(l1!1,l2!2), Lyn(U!3,SH2), Rec(a!2,b~Y!3), Rec(a!1,b~pY) @'pLb' Lig(l2!1,l1!2), Lyn(U!3,SH2), Rec(a!2,b~Y!3), Rec(a!1,b~Y) -> Lig(l2!1,l1!2), Lyn(U!3,SH2), Rec(a!2,b~Y!3), Rec(a!1,b~pY) @'pLb' # Transphosphorylation of gamma by constitutive Lyn Lig(l1!1,l2!2),Lyn(U!3,SH2),Rec(a!2,b~Y!3),Rec(a!1,g~Y) -> Lig(l1!1,l2!2),Lyn(U!3,SH2),Rec(a!2,b~Y!3),Rec(a!1,g~pY) @'pLg' Lig(l2!1,l1!2),Lyn(U!3,SH2),Rec(a!2,b~Y!3),Rec(a!1,g~Y) -> Lig(l2!1,l1!2),Lyn(U!3,SH2),Rec(a!2,b~Y!3),Rec(a!1,g~pY) @'pLg' # Lyn-receptor binding through SH2 domain Rec(b~pY) , Lyn(U,SH2) <-> Rec(b~pY!1),Lyn(U,SH2!1) @'kpLs', 'kmLs' # Fyn-receptor binding through SH2 domain Rec(b~pY) , Fyn(SH2) <-> Rec(b~pY!1),Fyn(SH2!1) @'kpF', 'kmF' # Transphosphorylation of beta by SH2-bound Lyn Lig(l1!1,l2!2),Lyn(U,SH2!3),Rec(a!2,b~pY!3),Rec(a!1,b~Y) -> Lig(l1!1,l2!2),Lyn(U,SH2!3),Rec(a!2,b~pY!3),Rec(a!1,b~pY) @'pLbs' Lig(l2!1,l1!2),Lyn(U,SH2!3),Rec(a!2,b~pY!3),Rec(a!1,b~Y) -> Lig(l2!1,l1!2),Lyn(U,SH2!3),Rec(a!2,b~pY!3),Rec(a!1,b~pY) @'pLbs' # Transphosphorylation of gamma by SH2-bound Lyn Lig(l1!1,l2!2),Lyn(U,SH2!3),Rec(a!2,b~pY!3),Rec(a!1,g~Y) -> Lig(l1!1,l2!2),Lyn(U,SH2!3),Rec(a!2,b~pY!3),Rec(a!1,g~pY) @'pLgs' Lig(l2!1,l1!2),Lyn(U,SH2!3),Rec(a!2,b~pY!3),Rec(a!1,g~Y) -> Lig(l2!1,l1!2),Lyn(U,SH2!3),Rec(a!2,b~pY!3),Rec(a!1,g~pY) @'pLgs' # Syk-receptor binding through tSH2 domain Rec(g~pY) , Syk(tSH2) <-> Rec(g~pY!1),Syk(tSH2!1) @'kpS'{0}, 'kmS' # Transphosphorylation of Lyn by constitutive Lyn Lig(l1!1,l2!2),Lyn(U!3,SH2),Rec(a!2,b~Y!3),Rec(a!1,b~pY!4),Lyn(SH2!4,a~Y) -> \ Lig(l1!1,l2!2),Lyn(U!3,SH2),Rec(a!2,b~Y!3),Rec(a!1,b~pY!4),Lyn(SH2!4,a~pY) @'pLS' Lig(l2!1,l1!2),Lyn(U!3,SH2),Rec(a!2,b~Y!3),Rec(a!1,b~pY!4),Lyn(SH2!4,a~Y) -> \ Lig(l2!1,l1!2),Lyn(U!3,SH2),Rec(a!2,b~Y!3),Rec(a!1,b~pY!4),Lyn(SH2!4,a~pY) @'pLS' # Transphosphorylation of Lyn by SH2-bound Lyn Lig(l1!1,l2!2),Lyn(U,SH2!3),Rec(a!2,b~pY!3),Rec(a!1,b~pY!4),Lyn(SH2!4,a~Y) -> \ Lig(l1!1,l2!2),Lyn(U,SH2!3),Rec(a!2,b~pY!3),Rec(a!1,b~pY!4),Lyn(SH2!4,a~pY) @'pLSs' Lig(l2!1,l1!2),Lyn(U,SH2!3),Rec(a!2,b~pY!3),Rec(a!1,b~pY!4),Lyn(SH2!4,a~Y) -> \ Lig(l2!1,l1!2),Lyn(U,SH2!3),Rec(a!2,b~pY!3),Rec(a!1,b~pY!4),Lyn(SH2!4,a~pY) @'pLSs' # Transphosphorylation of Fyn by constitutive Lyn Lig(l1!1,l2!2),Lyn(U!3,SH2),Rec(a!2,b~Y!3),Rec(a!1,b~pY!4),Fyn(SH2!4,a~Y) -> \ Lig(l1!1,l2!2),Lyn(U!3,SH2),Rec(a!2,b~Y!3),Rec(a!1,b~pY!4),Fyn(SH2!4,a~pY) @'pLF' Lig(l2!1,l1!2),Lyn(U!3,SH2),Rec(a!2,b~Y!3),Rec(a!1,b~pY!4),Fyn(SH2!4,a~Y) -> \ Lig(l2!1,l1!2),Lyn(U!3,SH2),Rec(a!2,b~Y!3),Rec(a!1,b~pY!4),Fyn(SH2!4,a~pY) @'pLF' # Transphosphorylation of Fyn by SH2-bound Lyn # KaSa has discovered that both following rules are wrong # Lyn has to be bound via SH2, not via U (since it is bound to a site with state pY) #Lig(l1!1,l2!2),Lyn(U!3,SH2),Rec(a!2,b~pY!3),Rec(a!1,b~pY!4),Fyn(SH2!4,a~Y) -> \ #Lig(l1!1,l2!2),Lyn(U!3,SH2),Rec(a!2,b~pY!3),Rec(a!1,b~pY!4),Fyn(SH2!4,a~pY) @'pLFs' #Lig(l2!1,l1!2),Lyn(U!3,SH2),Rec(a!2,b~pY!3),Rec(a!1,b~pY!4),Fyn(SH2!4,a~Y) -> \ #Lig(l2!1,l1!2),Lyn(U!3,SH2),Rec(a!2,b~pY!3),Rec(a!1,b~pY!4),Fyn(SH2!4,a~pY) @'pLFs' #correct rules: Lig(l1!1,l2!2),Lyn(U,SH2!3),Rec(a!2,b~pY!3),Rec(a!1,b~pY!4),Fyn(SH2!4,a~Y) -> \ Lig(l1!1,l2!2),Lyn(U,SH2!3),Rec(a!2,b~pY!3),Rec(a!1,b~pY!4),Fyn(SH2!4,a~pY) @'pLFs' Lig(l2!1,l1!2),Lyn(U,SH2!3),Rec(a!2,b~pY!3),Rec(a!1,b~pY!4),Fyn(SH2!4,a~Y) -> \ Lig(l2!1,l1!2),Lyn(U,SH2!3),Rec(a!2,b~pY!3),Rec(a!1,b~pY!4),Fyn(SH2!4,a~pY) @'pLFs' # Transphosphorylation of Syk by constitutive Lyn Lig(l1!1,l2!2),Lyn(U!3,SH2),Rec(a!2,b~Y!3),Rec(a!1,g~pY!4),Syk(tSH2!4,l~Y) -> \ Lig(l1!1,l2!2),Lyn(U!3,SH2),Rec(a!2,b~Y!3),Rec(a!1,g~pY!4),Syk(tSH2!4,l~pY) @'pLS' Lig(l2!1,l1!2),Lyn(U!3,SH2),Rec(a!2,b~Y!3),Rec(a!1,g~pY!4),Syk(tSH2!4,l~Y) -> \ Lig(l2!1,l1!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 Lig(l1!1,l2!2),Lyn(U,SH2!3),Rec(a!2,b~pY!3),Rec(a!1,g~pY!4),Syk(tSH2!4,l~Y) -> \ Lig(l1!1,l2!2),Lyn(U,SH2!3),Rec(a!2,b~pY!3),Rec(a!1,g~pY!4),Syk(tSH2!4,l~pY) @'pLSs' Lig(l2!1,l1!2),Lyn(U,SH2!3),Rec(a!2,b~pY!3),Rec(a!1,g~pY!4),Syk(tSH2!4,l~Y) -> \ Lig(l2!1,l1!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 Lig(l1!1,l2!2),Syk(tSH2!3,a~Y),Rec(a!2,g~pY!3),Rec(a!1,g~pY!4),Syk(tSH2!4,a~Y) -> \ Lig(l1!1,l2!2),Syk(tSH2!3,a~Y),Rec(a!2,g~pY!3),Rec(a!1,g~pY!4),Syk(tSH2!4,a~pY) @'pSS' Lig(l2!1,l1!2),Syk(tSH2!3,a~Y),Rec(a!2,g~pY!3),Rec(a!1,g~pY!4),Syk(tSH2!4,a~Y) -> \ Lig(l2!1,l1!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 Lig(l1!1,l2!2),Syk(tSH2!3,a~pY),Rec(a!2,g~pY!3),Rec(a!1,g~pY!4),Syk(tSH2!4,a~Y) -> \ Lig(l1!1,l2!2),Syk(tSH2!3,a~pY),Rec(a!2,g~pY!3),Rec(a!1,g~pY!4),Syk(tSH2!4,a~pY) @'pSSs' Lig(l2!1,l1!2),Syk(tSH2!3,a~pY),Rec(a!2,g~pY!3),Rec(a!1,g~pY!4),Syk(tSH2!4,a~Y) -> \ Lig(l2!1,l1!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 Rec(b~pY) -> Rec(b~Y) @'dm' # Dephosphorylation of Rec gamma Rec(g~pY) -> Rec(g~Y) @'dm' # Dephosphorylation of Syk at membrane Syk(tSH2!_,l~pY) -> Syk(tSH2!_,l~Y) @'dm' Syk(tSH2!_,a~pY) -> Syk(tSH2!_,a~Y) @'dm' # Dephosphorylation of Syk in cytosol Syk(tSH2,l~pY) -> Syk(tSH2,l~Y) @'dc' Syk(tSH2,a~pY) -> Syk(tSH2,a~Y) @'dc'