AXIN is phosphorylated in the destruction complex

Stable Identifier
R-HSA-5229343
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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In the absence of WNT signal, AXIN is a phosphoprotein; candidate kinases include both GSK3beta and CK1 (Ikeda et al, 1998; Willert et al, 1999; Jho et al, 1999; Yamamoto et al, 1999; Luo et al, 2007). Phosphorylation of AXIN is thought to increase its binding affinity for beta-catenin and GSK3beta, stabilizing the destruction complex and promoting efficient degradation of beta-catenin (Willert et al, 1999; Jho et al, 1999; Luo et al, 2007). A more recent model suggests that AXIN phosphorylation may disrupt an intramolecular interaction between its DIX domain and the beta-catenin binding region, which would otherwise keep AXIN in a 'closed' inactive state (Kim et al, 2013). Activation of the WNT pathway upon ligand binding favours dephosphorylation of AXIN by inactivating the kinases and allowing the steady state dephosphorylation by candidate phosphatases PP2A and PP1 to predominate (Willert et al, 1999; Luo et al, 2007; reviewed in Saito-Diaz et al, 2013).

Literature References
PubMed ID Title Journal Year
22101459 An anti-Wnt5a antibody suppresses metastasis of gastric cancer cells in vivo by inhibiting receptor-mediated endocytosis

Hanaki, H, Yamamoto, H, Sakane, H, Matsumoto, S, Ohdan, H, Sato, A, Kikuchi, A

Mol. Cancer Ther. 2012
23256519 The way Wnt works: Components and mechanism

Saito-Diaz, K, Chen, TW, Wang, X, Thorne, CA, Wallace, HA, Page-McCaw, A, Lee, E

Growth Factors 2013
10196136 Phosphorylation of axin, a Wnt signal negative regulator, by glycogen synthase kinase-3beta regulates its stability

Yamamoto, H, Kishida, S, Kishida, M, Ikeda, S, Takada, S, Kikuchi, A

J Biol Chem 1999
10421629 Wnt-induced dephosphorylation of axin releases beta-catenin from the axin complex

Willert, K, Shibamoto, S, Nusse, R

Genes Dev 1999
9482734 Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin

Ikeda, S, Kishida, S, Yamamoto, H, Murai, H, Koyama, S, Kikuchi, A

EMBO J. 1998
17318175 Protein phosphatase 1 regulates assembly and function of the beta-catenin degradation complex

Luo, W, Peterson, A, Garcia, BA, Coombs, G, Kofahl, B, Heinrich, R, Shabanowitz, J, Hunt, DF, Yost, HJ, Virshup, DM

EMBO J. 2007
10581160 A GSK3beta phosphorylation site in axin modulates interaction with beta-catenin and Tcf-mediated gene expression

Jho, E, Lomvardas, S, Costantini, F

Biochem Biophys Res Commun 1999
23579495 Wnt stabilization of ?-catenin reveals principles for morphogen receptor-scaffold assemblies

Kim, SE, Huang, H, Zhao, M, Zhang, X, Zhang, A, Semonov, MV, MacDonald, BT, Zhang, X, Garcia Abreu, J, Peng, L, He, X

Science 2013
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
protein serine/threonine kinase activity of AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complex [cytosol]
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Activity
Orthologous Events
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