Molecules

M1R(L,S228~u~p,S273~u~p,Arr,GRK,PP1,CK2)

M1R L S228 u p S273 u p Arr GRK PP1 CK2

Oxo(R)

Oxo R

Arrestin(RLP,MEK,PP2A)

Arrestin RLP MEK PP2A

MEK(Arr,ERK)

MEK Arr ERK

ERK(MEK,s~u,PP2A,PP1)

ERK MEK s u PP2A PP1

pERK(MEK,s~p,PP2A,PP1)

pERK MEK s p PP2A PP1

Oxo_EC()

Oxo_EC

PP2A(Arrestin,ERK)

PP2A Arrestin ERK

probe(site~u)

probe site u

phos_probe(Site0~p)

phos_probe Site0 p

GRK(RL)

GRK RL

PP1(RL)

PP1 RL

CK2(RL)

CK2 RL

Species

Oxo_EC()

Oxo_EC

M1R(L,S228~u,S273~u,Arr,GRK,PP1,CK2)

M1R L S228 u S273 u Arr GRK PP1 CK2

Oxo(R!1).M1R(L!1,S228~u,S273~u,Arr,GRK,PP1,CK2)

Oxo R M1R L S228 u S273 u Arr GRK PP1 CK2

Arrestin(RLP,MEK,PP2A)

Arrestin RLP MEK PP2A

Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK,PP2A)

Oxo R M1R L S228 p S273 p Arr GRK PP1 CK2 Arrestin RLP MEK PP2A

Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK!3,PP2A).MEK(Arr!3,ERK)

Oxo R M1R L S228 p S273 p Arr GRK PP1 CK2 Arrestin RLP MEK PP2A MEK Arr ERK

ERK(MEK,s~u,PP2A,PP1)

ERK MEK s u PP2A PP1

MEK(Arr,ERK)

MEK Arr ERK

PP2A(Arrestin,ERK)

PP2A Arrestin ERK

pERK(MEK,s~p,PP2A,PP1)

pERK MEK s p PP2A PP1

Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK!3,PP2A).MEK(Arr!3,ERK!4).ERK(MEK!4,s~u,PP2A,PP1)

Oxo R M1R L S228 p S273 p Arr GRK PP1 CK2 Arrestin RLP MEK PP2A MEK Arr ERK ERK MEK s u PP2A PP1

Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK!3,PP2A).MEK(Arr!3,ERK!4).pERK(MEK!4,s~p,PP2A,PP1)

Oxo R M1R L S228 p S273 p Arr GRK PP1 CK2 Arrestin RLP MEK PP2A MEK Arr ERK pERK MEK s p PP2A PP1

Oxo(R!1).M1R(L!1,S228~u,S273~u,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK,PP2A)

Oxo R M1R L S228 u S273 u Arr GRK PP1 CK2 Arrestin RLP MEK PP2A

Oxo(R!1).M1R(L!1,S228~u,S273~u,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK,PP2A!3).PP2A(Arrestin!3,ERK)

Oxo R M1R L S228 u S273 u Arr GRK PP1 CK2 Arrestin RLP MEK PP2A PP2A Arrestin ERK

probe(site~u)

probe site u

phos_probe(Site0~p)

phos_probe Site0 p

GRK(RL)

GRK RL

Oxo(R!1).M1R(L!1,S228~u,S273~u,Arr,GRK!2,PP1,CK2).GRK(RL!2)

Oxo R M1R L S228 u S273 u Arr GRK PP1 CK2 GRK RL

Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr,GRK!2,PP1,CK2).GRK(RL!2)

Oxo R M1R L S228 p S273 p Arr GRK PP1 CK2 GRK RL

Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr,GRK,PP1,CK2)

Oxo R M1R L S228 p S273 p Arr GRK PP1 CK2

Oxo(R!1).M1R(L!1,S228~u,S273~u,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK,PP2A!3).PP2A(Arrestin!3,ERK!4).pERK(MEK,s~p,PP2A!4,PP1)

Oxo R M1R L S228 u S273 u Arr GRK PP1 CK2 Arrestin RLP MEK PP2A PP2A Arrestin ERK pERK MEK s p PP2A PP1

Oxo(R!1).M1R(L!1,S228~u,S273~u,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK,PP2A!3).PP2A(Arrestin!3,ERK!4).ERK(MEK,s~u,PP2A!4,PP1)

Oxo R M1R L S228 u S273 u Arr GRK PP1 CK2 Arrestin RLP MEK PP2A PP2A Arrestin ERK ERK MEK s u PP2A PP1

Oxo(R!1).M1R(L!1,S228~u,S273~u,Arr,GRK,PP1!2,CK2).PP1(RL!2)

Oxo R M1R L S228 u S273 u Arr GRK PP1 CK2 PP1 RL

PP1(RL)

PP1 RL

CK2(RL)

CK2 RL

Oxo(R!1).M1R(L!1,S228~u,S273~u,Arr,GRK,PP1,CK2!2).CK2(RL!2)

Oxo R M1R L S228 u S273 u Arr GRK PP1 CK2 CK2 RL

Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr,GRK,PP1,CK2!2).CK2(RL!2)

Oxo R M1R L S228 p S273 p Arr GRK PP1 CK2 CK2 RL

Observables

O0_M1R_tot M1R(L,S228,S273,Arr,GRK,PP1,CK2)

M1R L S228 S273 Arr GRK PP1 CK2

O0_Oxo_EC Oxo(R)

Oxo R

O0_Arrestin Arrestin(RLP,MEK,PP2A)

Arrestin RLP MEK PP2A

O0_RLPPA Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK,PP2A)

Oxo R M1R L S228 p S273 p Arr GRK PP1 CK2 Arrestin RLP MEK PP2A

O0_MEK MEK(Arr,ERK)

MEK Arr ERK

O0_ERK ERK(MEK,s~u,PP2A,PP1)

ERK MEK s u PP2A PP1

O0_pERK pERK(MEK,s~p,PP2A,PP1)

pERK MEK s p PP2A PP1

O0_RLPPA_M Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK!3,PP2A).MEK(Arr!3,ERK)

Oxo R M1R L S228 p S273 p Arr GRK PP1 CK2 Arrestin RLP MEK PP2A MEK Arr ERK

O0_RLPP Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr,GRK,PP1,CK2)

Oxo R M1R L S228 p S273 p Arr GRK PP1 CK2

O0_RLA Oxo(R!1).M1R(L!1,S228~u,S273~u,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK,PP2A)

Oxo R M1R L S228 u S273 u Arr GRK PP1 CK2 Arrestin RLP MEK PP2A

O0_Oxo_EC_tot Oxo_EC()

Oxo_EC

O0_PP2A_tot PP2A(Arrestin,ERK)

PP2A Arrestin ERK

O0_RLAPP2A Oxo(R!1).M1R(L!1,S228~u,S273~u,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK,PP2A!3).PP2A(Arrestin!3,ERK)

Oxo R M1R L S228 u S273 u Arr GRK PP1 CK2 Arrestin RLP MEK PP2A PP2A Arrestin ERK

O0_RLppAME Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK!3,PP2A).MEK(Arr!3,ERK!4).ERK(MEK!4,s~u)

Oxo R M1R L S228 p S273 p Arr GRK PP1 CK2 Arrestin RLP MEK PP2A MEK Arr ERK ERK MEK s u ?PP2A ?PP1

O0_RLppAMpE Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK!3,PP2A).MEK(Arr!3,ERK!4).pERK(MEK!4,s~p)

Oxo R M1R L S228 p S273 p Arr GRK PP1 CK2 Arrestin RLP MEK PP2A MEK Arr ERK pERK MEK s p ?PP2A ?PP1

O0_probe_tot probe()

probe site ?u

O0_phos_probe_tot phos_probe()

phos_probe Site0 ?p

O0_GRK_tot GRK()

GRK ?RL

O0_PP1_tot PP1()

PP1 ?RL

O0_CK2_tot CK2()

CK2 ?RL

Reaction Rules

Oxo(R) + M1R(L,S228~u,S273~u,Arr,GRK,PP1,CK2) <-> Oxo(R!1).M1R(L!1,S228~u,S273~u,Arr,GRK,PP1,CK2)

Oxo ⬇⬆R ⬇⬆ M1R ⬇⬆L S228 u S273 u Arr GRK PP1 CK2

Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr,GRK,PP1,CK2) + Arrestin(RLP,MEK,PP2A) <-> Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK,PP2A)

Oxo R M1R L S228 p S273 p ⬇⬆Arr GRK PP1 CK2 ⬇⬆ Arrestin ⬇⬆RLP MEK PP2A

Oxo(R!1).M1R(L!1,S228~u,S273~u,Arr,GRK,PP1,CK2) + Arrestin(RLP,MEK,PP2A) <-> Oxo(R!1).M1R(L!1,S228~u,S273~u,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK,PP2A)

Oxo R M1R L S228 u S273 u ⬇⬆Arr GRK PP1 CK2 ⬇⬆ Arrestin ⬇⬆RLP MEK PP2A

Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr,GRK,PP1,CK2) -> Oxo(R!1).M1R(L!1,S228~u,S273~u,Arr,GRK,PP1,CK2)

Oxo R M1R L S228 u p take one or more branches, once each, in any order S273 u p take one or more branches, once each, in any order Arr GRK PP1 CK2

Oxo(R!1).M1R(L!1,S228~u,S273~u,Arr,GRK!2,PP1,CK2).GRK(RL!2) -> Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr,GRK!2,PP1,CK2).GRK(RL!2)

Oxo R M1R L S228 u p take all branches, once each, in any order S273 u p take all branches, once each, in any order Arr GRK PP1 CK2 GRK RL

Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK,PP2A) + MEK(Arr,ERK) <-> Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK!3,PP2A).MEK(Arr!3,ERK)

Oxo R M1R L S228 p S273 p Arr GRK PP1 CK2 Arrestin RLP ⬇⬆MEK PP2A ⬇⬆ MEK ⬇⬆Arr ERK

Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK!3,PP2A).MEK(Arr!3,ERK) + ERK(MEK,s~u,PP2A,PP1) <-> Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK!3,PP2A).MEK(Arr!3,ERK!4).ERK(MEK!4,s~u,PP2A,PP1)

Oxo R M1R L S228 p S273 p Arr GRK PP1 CK2 Arrestin RLP MEK PP2A MEK Arr ⬇⬆ERK ⬇⬆ ERK ⬇⬆MEK s u PP2A PP1

Oxo_EC() -> Oxo(R)

Oxo_EC degraded Oxo R synthesized

Oxo(R!1).M1R(L!1,S228~u,S273~u,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK,PP2A) + PP2A(Arrestin,ERK) <-> Oxo(R!1).M1R(L!1,S228~u,S273~u,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK,PP2A!3).PP2A(Arrestin!3,ERK)

Oxo R M1R L S228 u S273 u Arr GRK PP1 CK2 Arrestin RLP MEK ⬇⬆PP2A ⬇⬆ PP2A ⬇⬆Arrestin ERK

Oxo(R!1).M1R(L!1,S228~u,S273~u,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK,PP2A!3).PP2A(Arrestin!3,ERK) + pERK(MEK,s~p,PP2A,PP1) <-> Oxo(R!1).M1R(L!1,S228~u,S273~u,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK,PP2A!3).PP2A(Arrestin!3,ERK) + ERK(MEK,s~u,PP2A,PP1)

Oxo R M1R L S228 u S273 u Arr GRK PP1 CK2 Arrestin RLP MEK PP2A PP2A Arrestin ERK pERK MEK s p PP2A PP1 degraded ERK MEK s u PP2A PP1 synthesized

Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK!3,PP2A).MEK(Arr!3,ERK!4).ERK(MEK!4,s~u,PP2A,PP1) <-> Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK!3,PP2A).MEK(Arr!3,ERK!4).pERK(MEK!4,s~p,PP2A,PP1)

Oxo R M1R L S228 p S273 p Arr GRK PP1 CK2 Arrestin RLP MEK PP2A MEK Arr ERK ERK MEK s u PP2A PP1 degraded pERK MEK s p PP2A PP1 synthesized

Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK!3,PP2A).MEK(Arr!3,ERK!4).pERK(MEK!4,s~p,PP2A,PP1) <-> Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr!2,GRK,PP1,CK2).Arrestin(RLP!2,MEK!3,PP2A).MEK(Arr!3,ERK) + pERK(MEK,s~p,PP2A,PP1)

Oxo R M1R L S228 p S273 p Arr GRK PP1 CK2 Arrestin RLP MEK PP2A MEK Arr ⬆⬇ERK ⬆⬇ pERK ⬆⬇MEK s p PP2A PP1

Oxo(R!1).M1R(L!1,S228~u,S273~u,Arr,GRK,PP1,CK2) + GRK(RL) <-> Oxo(R!1).M1R(L!1,S228~u,S273~u,Arr,GRK!2,PP1,CK2).GRK(RL!2)

Oxo R M1R L S228 u S273 u Arr ⬇⬆GRK PP1 CK2 ⬇⬆ GRK ⬇⬆RL

Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr,GRK!2,PP1,CK2).GRK(RL!2) <-> Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr,GRK,PP1,CK2) + GRK(RL)

Oxo R M1R L S228 p S273 p Arr ⬆⬇GRK PP1 CK2 ⬆⬇ GRK ⬆⬇RL

ERK(MEK,s~u,PP2A,PP1) <-> pERK(MEK,s~p,PP2A,PP1)

ERK MEK s u PP2A PP1 degraded pERK MEK s p PP2A PP1 synthesized

pERK(MEK,s~p,PP2A,PP1) + probe(site~u) <-> pERK(MEK,s~p,PP2A,PP1) + phos_probe(Site0~p)

pERK MEK s p PP2A PP1 probe site u degraded phos_probe Site0 p synthesized

Oxo(R!1).M1R(L!1,S228~u,S273~u,Arr,GRK,PP1,CK2) + CK2(RL) <-> Oxo(R!1).M1R(L!1,S228~u,S273~u,Arr,GRK,PP1,CK2!2).CK2(RL!2)

Oxo R M1R L S228 u S273 u Arr GRK PP1 ⬇⬆CK2 ⬇⬆ CK2 ⬇⬆RL

Oxo(R!1).M1R(L!1,S228~u,S273~u,Arr,GRK,PP1,CK2!2).CK2(RL!2) -> Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr,GRK,PP1,CK2!2).CK2(RL!2)

Oxo R M1R L S228 u p take all branches, once each, in any order S273 u p take all branches, once each, in any order Arr GRK PP1 CK2 CK2 RL

Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr,GRK,PP1,CK2!2).CK2(RL!2) <-> Oxo(R!1).M1R(L!1,S228~p,S273~p,Arr,GRK,PP1,CK2) + CK2(RL)

Oxo R M1R L S228 p S273 p Arr GRK PP1 ⬆⬇CK2 ⬆⬇ CK2 ⬆⬇RL