Reactome | AXIN is phosphorylated in the destruction complex

AXIN is phosphorylated in the destruction complex

Stable Identifier

R-HSA-5229343

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

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AXIN is phosphorylated in the destruction complex

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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