Molecules

AXIN(rgs,gid,b,e)

AXIN rgs gid b e

GSK3b(a)

GSK3b a

APC(a15,a20~U~P,s)

APC a15 a20 U P s

bCat(s33s37~U~P,s45~U~P,ARM34,ARM59,ss~l~d)

bCat s33s37 U P s45 U P ARM34 ARM59 ss l d

CK1a(e)

CK1a e

dead()

dead

I()

I

Species

bCat(s33s37~U,s45~U,,ARM34,ARM59,ss~l)

bCat s33s37 U s45 U ARM34 ARM59 ss l

APC(a15,a20~U,s)

APC a15 a20 U s

AXIN(rgs,gid,b,e)

AXIN rgs gid b e

GSK3b(a)

GSK3b a

CK1a(e)

CK1a e

I()

I

dead()

dead

Observables

bcat_tot bCat(ss~l)

bCat s33s37 U ?P s45 U ?P ?ARM34 ?ARM59 ss l

bCat_pS45 bCat(s45~P,ss~l)

bCat s33s37 U ?P s45 P ?ARM34 ?ARM59 ss l

bCat_pS33S37 bCat(s33s37~P,ss~l)

bCat s33s37 P s45 U ?P ?ARM34 ?ARM59 ss l

APC_p20a APC(a20~P!?)

APC ?a15 a20 ?P ?s

BCat_Axin bCat(ARM34!1,ss~l).AXIN(b!1)

bCat s33s37 U ?P s45 U ?P ARM34 ?ARM59 ss l AXIN ?rgs ?gid b ?e

Reaction Rules


Binding of beta-catenin ARM repeats 5-9 to APC 15-aa repeats (Arrow 1)

bCat(ARM59,ss~l) + APC(a15) <-> bCat(ARM59!1,ss~l).APC(a15!1)

bCat s33s37 U ?P s45 U ?P ?ARM34 ⬇⬆ARM59 ss l ⬇⬆ APC ⬇⬆a15 a20 U ?P ?s

bCat(ARM59,ARM34!1,ss~l).AXIN(b!1,rgs!2).APC(a15,s!2) <-> bCat(ARM59!3,ARM34!1,ss~l).AXIN(b!1,rgs!2).APC(a15!3,s!2)

bCat s33s37 U ?P s45 U ?P ARM34 ⬇⬆ARM59 ss l AXIN rgs ?gid b ?e APC ⬇⬆a15 a20 U ?P s

bCat(ARM59,ARM34!1).APC(a15,a20~P!1) <-> bCat(ARM59!2,ARM34!1).APC(a15!2,a20~P!1)

bCat s33s37 U ?P s45 U ?P ARM34 ⬇⬆ARM59 ss l ?d APC ⬇⬆a15 a20 P ?s

Binding of beta-catenin ARM repeats 3-4 to phosphorylated APC 20-aa repeats (Arrow 2)

bCat(ARM34,ss~l) + APC(a20~P) <-> bCat(ARM34!1,ss~l).APC(a20~P!1)

bCat s33s37 U ?P s45 U ?P ⬇⬆ARM34 ?ARM59 ss l ⬇⬆ APC ?a15 a20 ⬇⬆P ?s

bCat(ARM59!1,ARM34).APC(a15!1,a20~P) <-> bCat(ARM59!1,ARM34!2).APC(a15!1,a20~P!2)

bCat s33s37 U ?P s45 U ?P ⬇⬆ARM34 ARM59 ss l ?d APC a15 a20 ⬇⬆P ?s

Binding of beta-Catenin ARM repeats 3 and 4 with Axin (Arrow 3)

bCat(ARM34,ss~l) + AXIN(b) <-> bCat(ARM34!1,ss~l).AXIN(b!1)

bCat s33s37 U ?P s45 U ?P ⬇⬆ARM34 ?ARM59 ss l ⬇⬆ AXIN ?rgs ?gid ⬇⬆b ?e

bCat(ARM59!1,ARM34,ss~l).AXIN(b,rgs!2).APC(a15!1,s!2) <-> bCat(ARM59!1,ARM34!3,ss~l).AXIN(b!3,rgs!2).APC(a15!1,s!2)

bCat s33s37 U ?P s45 U ?P ⬇⬆ARM34 ARM59 ss l AXIN rgs ?gid ⬇⬆b ?e APC a15 a20 U ?P s

Binding of APC SAMP repeats to Axin RGS domain (Arrow 4)

APC(a20~U,s) + AXIN(rgs) <-> APC(a20~U,s!1).AXIN(rgs!1)

APC ?a15 a20 U ⬇⬆s ⬇⬆ AXIN ⬇⬆rgs ?gid ?b ?e

APC(a20~P,s) + AXIN(rgs) <-> APC(a20~P,s!1).AXIN(rgs!1)

APC ?a15 a20 P ⬇⬆s ⬇⬆ AXIN ⬇⬆rgs ?gid ?b ?e

APC(a20~P!+,s) + AXIN(rgs) <-> APC(a20~P!+,s!1).AXIN(rgs!1)

APC ?a15 a20 P ⬇⬆s ⬇⬆ AXIN ⬇⬆rgs ?gid ?b ?e

APC(a15!1,a20~U,s).bCat(ARM59!1,ARM34!2,ss~l).AXIN(rgs,b!2) <-> APC(a15!1,a20~U,s!3).bCat(ARM59!1,ARM34!2,ss~l).AXIN(rgs!3,b!2)

APC a15 a20 U ⬇⬆s bCat s33s37 U ?P s45 U ?P ARM34 ARM59 ss l AXIN ⬇⬆rgs ?gid b ?e

APC(a15!1,a20~P,s).bCat(ARM59!1,ARM34!2,ss~l).AXIN(rgs,b!2) <-> APC(a15!1,a20~P,s!3).bCat(ARM59!1,ARM34!2,ss~l).AXIN(rgs!3,b!2)

APC a15 a20 P ⬇⬆s bCat s33s37 U ?P s45 U ?P ARM34 ARM59 ss l AXIN ⬇⬆rgs ?gid b ?e

APC(a15!1,a20~P!+,s).bCat(ARM59!1,ARM34!2,ss~l).AXIN(rgs,b!2) <-> APC(a15!1,a20~P!+,s!3).bCat(ARM59!1,ARM34!2,ss~l).AXIN(rgs!3,b!2)

APC a15 a20 P ⬇⬆s bCat s33s37 U ?P s45 U ?P ARM34 ARM59 ss l AXIN ⬇⬆rgs ?gid b ?e

Binding of GSK-3beta to AXIN GID domain (Arrow 5)

GSK3b(a) + AXIN(gid) <-> GSK3b(a!1).AXIN(gid!1)

GSK3b ⬇⬆a ⬇⬆ AXIN ?rgs ⬇⬆gid ?b ?e

Binding of CK1alpha to Axin (Arrow 6)

AXIN(e) + CK1a(e) <-> AXIN(e!1).CK1a(e!1)

AXIN ?rgs ?gid ?b ⬇⬆e ⬇⬆ CK1a ⬇⬆e

Phosphorylation of S45 of beta-catenin by CK1alpha (Arrow 7)

bCat(s45~U,ss~l).CK1a() -> bCat(s45~P,ss~l).CK1a()

bCat s33s37 U ?P s45 U P take all branches, once each, in any order⬇ ?ARM34 ?ARM59 ss l CK1a ?e

Phosphorylation of S33/S37 of beta-catenin by GSK-3beta (Arrow 8)

bCat(s33s37~U,s45~P,ss~l).GSK3b() -> bCat(s33s37~P,s45~P,ss~l).GSK3b()

bCat s33s37 U P take all branches, once each, in any order⬇ s45 P ?ARM34 ?ARM59 ss l GSK3b ?a

Phosphorylation of APC 20-aa repeat by CK1epsilon (implicit) and GSK-3beta (Arrows 9 and 10)

APC(a20~U).GSK3b() -> APC(a20~P).GSK3b()

APC ?a15 a20 U P take all branches, once each, in any order⬇ ?s GSK3b ?a

Dephsophorylation of beta-catenin

bCat(s45~P,ss~l) -> bCat(s45~U,ss~l)

bCat s33s37 U ?P s45 U P take one or more branches, once each, in any order⬆ ?ARM34 ?ARM59 ss l

bCat(s33s37~P,ss~l) -> bCat(s33s37~U,ss~l)

bCat s33s37 U P take one or more branches, once each, in any order⬆ s45 U ?P ?ARM34 ?ARM59 ss l

Dephoshporylation of APC

APC(a20~P).AXIN() -> APC(a20~U).AXIN()

APC ?a15 a20 U P take one or more branches, once each, in any order⬆ ?s AXIN ?rgs ?gid ?b ?e

b-catenin synthesis

I() -> I() + bCat(s33s37~U,s45~U,ARM59,ARM34,ss~l)

I bCat s33s37 U s45 U ARM34 ARM59 ss l synthesized

Degradation of beta-catenin not phosphorylated at S33/S37

bCat(s33s37~U,ss~l) -> bCat(s33s37~U,ss~d)

bCat s33s37 U s45 U ?P ?ARM34 ?ARM59 ss l d take all branches, once each, in any order⬇

Degradation of beta-catenin phosphorylated at S33/S37

bCat(s33s37~P,ss~l) -> bCat(s33s37~P,ss~d)

bCat s33s37 P s45 U ?P ?ARM34 ?ARM59 ss l d take all branches, once each, in any order⬇

(Assumed) rapid dissociation of beta-catenin associated proteins upon degradation of beta-catenin

bCat(ARM59!1,ss~d).APC(a15!1) -> bCat(ARM59,ss~d) + APC(a15)

bCat s33s37 U ?P s45 U ?P ?ARM34 ⬆ARM59 ss d ⬆ APC ⬆a15 a20 U ?P ?s

bCat(ARM59!1,ss~d).APC(a15!1) -> bCat(ARM59,ss~d).APC(a15)

bCat s33s37 U ?P s45 U ?P ?ARM34 ⬆ARM59 ss d APC ⬆a15 a20 U ?P ?s

bCat(ARM34!1,ss~d).APC(a20~P!1) -> bCat(ARM34,ss~d) + APC(a20~P)

bCat s33s37 U ?P s45 U ?P ⬆ARM34 ?ARM59 ss d ⬆ APC ?a15 a20 ⬆P ?s

bCat(ARM34!1,ss~d).AXIN(b!1) -> bCat(ARM34,ss~d) + AXIN(b)

bCat s33s37 U ?P s45 U ?P ⬆ARM34 ?ARM59 ss d ⬆ AXIN ?rgs ?gid ⬆b ?e

bCat(ARM34!1,ss~d).AXIN(b!1) -> bCat(ARM34,ss~d).AXIN(b)

bCat s33s37 U ?P s45 U ?P ⬆ARM34 ?ARM59 ss d AXIN ?rgs ?gid ⬆b ?e