Reactome: A Curated Pathway Database

disassembly of the destruction complex and recruitment of AXIN to the membrane (R-HSA-4641262)

Species Homo sapiens

Summation

Upon stimulation with WNT ligand, AXIN and GSK3beta are recruited to the plasma membrane through interaction with DVL (Tamai et al, 2004; Mao et al, 2001; reviewed in He et al, 2004). Polymerization of membrane-associated DVL and GSK3beta- and CSNK1-mediated phosphorylation of LRP5/6 establish a feed-forward mechanism for enhanced membrane recruitment of AXIN upon WNT signaling (Tamai et al, 2004; Cong et al, 2004; Zeng et al, 2005; Bilic et al, 2007). In Xenopus oocytes, but not necessarily all sytems, AXIN is present in limiting concentrations and is considered rate limiting for the assembly of the destruction complex (Lee et al, 2003; Benchabane et al, 2008; Tan et al, 2012; reviewed in MacDonald et al, 2009). The recruitment of AXIN away from the destruction complex upon WNT stimulation effectively destabilizes the destruction complex and contributes to the accumulation of free beta-catenin (Kikuchi, 1999; Lee et al, 2003). AXIN association with the destruction complex is also regulated by phosphorylation. In the active destruction complex, AXIN is phosphorylated by GSK3beta; dephosphorylation by protein phosphatase 1 (PP1) or protein phosphatase 2A (PP2A) destabilizes the interaction of AXIN with the other components of the destruction complex and promotes its disassembly (Luo et al, 2007; Willert et al, 1999; Jho et al, 1999). Free AXIN is also subject to degradation by the 26S proteasome in a manner that depends on the poly-ADP-ribosylating enzymes tankyrase 1 and 2 (Huang et al, 2009).

Locations in the PathwayBrowser
Additional Information
GO Biological Process positive regulation of canonical Wnt signaling pathway (0090263)
Cross References
Database Identifier
BioModels Database BIOMD0000000149
Literature References
pubMedId Title Journal Year
16341017 A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation Nature 2005
14731402 A mechanism for Wnt coreceptor activation Mol Cell 2004
11336703 Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway Mol Cell 2001
15084453 LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way Development 2004
10421629 Wnt-induced dephosphorylation of axin releases beta-catenin from the axin complex Genes Dev 1999
10581160 A GSK3beta phosphorylation site in axin modulates interaction with beta-catenin and Tcf-mediated gene expression Biochem Biophys Res Commun 1999
19759537 Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling Nature 2009
15459103 Wnt signals across the plasma membrane to activate the beta-catenin pathway by forming oligomers containing its receptors, Frizzled and LRP Development 2004
17569865 Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation Science 2007
17318175 Protein phosphatase 1 regulates assembly and function of the beta-catenin degradation complex EMBO J. 2007
10647780 Modulation of Wnt signaling by Axin and Axil Cytokine Growth Factor Rev. 1999
14551908 The roles of APC and Axin derived from experimental and theoretical analysis of the Wnt pathway PLoS Biol 2003
22363759 Wnt signalling pathway parameters for mammalian cells PLoS ONE 2012
18234723 Adenomatous polyposis coli is present near the minimal level required for accurate graded responses to the Wingless morphogen Development 2008
19619488 Wnt/beta-catenin signaling: components, mechanisms, and diseases Dev Cell 2009