Reactome | Beta-catenin is released from the destruction complex

Beta-catenin is released from the destruction complex

Stable Identifier

R-HSA-201685

Type

Reaction [dissociation]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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Beta-catenin is released from the destruction complex

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Stimulation of the WNT pathway results in the recruitment of the GSK3beta:AXIN complex to the membrane (Willert et al, 1999; Schwarz Romond et al, 2007; Bilic et al, 2007; reviewed in Saito-Diaz et al, 2013). Activation of WNT signaling is believed to transiently inhibit GSK3beta kinase activity preventing its phosphorylation of beta-catenin (described in detail in the pathway "Degradation of beta-catenin by the destruction complex"; Piao et al, 2008; reviewed in Saito-Diaz et al, 2013). Inhibition of GSK3beta activity also prevents phosphorylation of AXIN allowing the constitutive dephosphorylation of AXIN at GSK3beta-dependent phosphorylation sites by PP2A predominate. This is believed to weaken the interaction between AXIN and beta-catenin (Willert et al, 1999). AXIN has also been shown to be dephosphorylated by PP1 at several serinve residues initially phosphorylated by CSNK1. The dephosphorylation by PP1 weakens the interaction between AXIN-GSK3beta and inhibits beta-catenin phosphorylation/degradation (Luo et al, 2007; reviewed in Huang et al, 2008). A recent study suggests that sustained inactivation of GSK3beta may result from its sequestration in multivesicular bodies (Taelman et al, 2010; reviewed in Niehrs and Acebon, 2010; Schuldt, 2011). Together, these changes destabilize the destruction complex and allow beta-catenin to accumulate.

Literature References

PubMed ID	Title	Journal	Year
19107203	Direct inhibition of GSK3beta by the phosphorylated cytoplasmic domain of LRP6 in Wnt/beta-catenin signaling Park, BJ, Lee, SH, Ha, NC, Oh, S, Lee, SJ, Lee, J, Yum, S, Weis, WI, Stamos, JL, Xu, Y, Han, JK, Kim, H, Piao, S	PLoS ONE	2008
17529994	The DIX domain of Dishevelled confers Wnt signaling by dynamic polymerization Kikuchi, A, Shibata, N, Higuchi, Y, Schwarz-Romond, T, Bienz, M, Fiedler, M, Butler, PJ	Nat. Struct. Mol. Biol.	2007
21183070	Wnt signaling: multivesicular bodies hold GSK3 captive Niehrs, C, Acebron, SP	Cell	2010
23256519	The way Wnt works: Components and mechanism Wang, X, Wallace, HA, Page-McCaw, A, Lee, E, Thorne, CA, Chen, TW, Saito-Diaz, K	Growth Factors	2013
18339531	Wnt/beta-catenin signaling: new (and old) players and new insights Huang, H, He, X	Curr. Opin. Cell Biol.	2008
21183076	Wnt signaling requires sequestration of glycogen synthase kinase 3 inside multivesicular endosomes Vorwald, PP, Taelman, VF, Fuentealba, LC, Plouhinec, JL, Dobrowolski, R, Sabatini, DD, Gumper, I, De Robertis, EM	Cell	2010
17569865	Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation Niehrs, C, Cruciat, CM, Bienz, M, Zimmermann, T, Huang, YL, Bilic, J, Davidson, G	Science	2007
10421629	Wnt-induced dephosphorylation of axin releases beta-catenin from the axin complex Willert, K, Nusse, R, Shibamoto, S	Genes Dev	1999
17318175	Protein phosphatase 1 regulates assembly and function of the beta-catenin degradation complex Garcia, BA, Shabanowitz, J, Peterson, A, Coombs, G, Virshup, DM, Luo, W, Yost, HJ, Hunt, DF, Heinrich, R, Kofahl, B	EMBO J.	2007
21252990	Membrane trafficking: a GSK3 lockdown Schuldt, A	Nat. Rev. Mol. Cell Biol.	2011