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(ss~l)

bCat s33s37 U P s45 U P ARM34 ARM59 ss l

bCat(s45~P,ss~l)

bCat s33s37 U P s45 P ARM34 ARM59 ss l

bCat(s33s37~P,ss~l)

bCat s33s37 P s45 U P ARM34 ARM59 ss l

APC(a20~P!?)

APC a15 a20 P s

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

bCat s33s37 U P s45 U P 1ARM34 ARM59 ss l AXIN rgs gid 1b 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 1 ⬆⬇ARM59 ss l APC 1 ⬆⬇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 1ARM34 3 ⬆⬇ARM59 ss l AXIN 2rgs gid 1b e APC 3 ⬆⬇a15 a20 U P 2s

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 1ARM34 2 ⬆⬇ARM59 ss l d APC 2 ⬆⬇a15 a20 1P 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 1 ⬆⬇ARM34 ARM59 ss l APC a15 a20 1 ⬆⬇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 2 ⬆⬇ARM34 1ARM59 ss l d APC 1a15 a20 2 ⬆⬇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 1 ⬆⬇ARM34 ARM59 ss l AXIN rgs gid 1 ⬆⬇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 3 ⬆⬇ARM34 1ARM59 ss l AXIN 2rgs gid 3 ⬆⬇b e APC 1a15 a20 U P 2s
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 1 ⬆⬇s AXIN 1 ⬆⬇rgs gid b e

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

APC a15 a20 P 1 ⬆⬇s AXIN 1 ⬆⬇rgs gid b e

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

APC a15 a20 P 1 ⬆⬇s AXIN 1 ⬆⬇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 1a15 a20 U 3 ⬆⬇s bCat s33s37 U P s45 U P 2ARM34 1ARM59 ss l AXIN 3 ⬆⬇rgs gid 2b 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 1a15 a20 P 3 ⬆⬇s bCat s33s37 U P s45 U P 2ARM34 1ARM59 ss l AXIN 3 ⬆⬇rgs gid 2b 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 1a15 a20 P 3 ⬆⬇s bCat s33s37 U P s45 U P 2ARM34 1ARM59 ss l AXIN 3 ⬆⬇rgs gid 2b e
Binding of GSK-3beta to AXIN GID domain (Arrow 5)

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

GSK3b 1 ⬆⬇a AXIN rgs 1 ⬆⬇gid b e
Binding of CK1alpha to Axin (Arrow 6)

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

AXIN rgs gid b 1 ⬆⬇e CK1a 1 ⬆⬇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 synthesisDegradation 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 1 ⬆ARM59 ss d APC 1 ⬆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 1 ⬆ARM59 ss d APC 1 ⬆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 1 ⬆ARM34 ARM59 ss d APC a15 a20 1 ⬆P s

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

bCat s33s37 U P s45 U P 1 ⬆ARM34 ARM59 ss d AXIN rgs gid 1 ⬆b e

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

bCat s33s37 U P s45 U P 1 ⬆ARM34 ARM59 ss d AXIN rgs gid 1 ⬆b e