Beta-catenin is released from the destruction complex

Stable Identifier
R-HSA-201685
Type
Reaction [dissociation]
Species
Homo sapiens
Compartment
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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
17529994 The DIX domain of Dishevelled confers Wnt signaling by dynamic polymerization

Schwarz-Romond, T, Fiedler, M, Shibata, N, Butler, PJ, Kikuchi, A, Higuchi, Y, Bienz, M

Nat. Struct. Mol. Biol. 2007
19107203 Direct inhibition of GSK3beta by the phosphorylated cytoplasmic domain of LRP6 in Wnt/beta-catenin signaling

Piao, S, Lee, SH, Kim, H, Yum, S, Stamos, JL, Xu, Y, Lee, SJ, Lee, J, Oh, S, Han, JK, Park, BJ, Weis, WI, Ha, NC

PLoS ONE 2008
21183070 Wnt signaling: multivesicular bodies hold GSK3 captive

Niehrs, C, Acebron, SP

Cell 2010
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
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

Taelman, VF, Dobrowolski, R, Plouhinec, JL, Fuentealba, LC, Vorwald, PP, Gumper, I, Sabatini, DD, De Robertis, EM

Cell 2010
17569865 Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation

Bilic, J, Huang, YL, Davidson, G, Zimmermann, T, Cruciat, CM, Bienz, M, Niehrs, C

Science 2007
10421629 Wnt-induced dephosphorylation of axin releases beta-catenin from the axin complex

Willert, K, Shibamoto, S, Nusse, R

Genes Dev 1999
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
21252990 Membrane trafficking: a GSK3 lockdown

Schuldt, A

Nat. Rev. Mol. Cell Biol. 2011
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