Reactome | Disassembly of the destruction complex and recruitment of AXIN to the membrane

Disassembly of the destruction complex and recruitment of AXIN to the membrane

Stable Identifier

R-HSA-4641262

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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Disassembly of the destruction complex and recruitment of AXIN to the membrane

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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).

Literature References

PubMed ID	Title	Journal	Year
18234723	Adenomatous polyposis coli is present near the minimal level required for accurate graded responses to the Wingless morphogen Hughes, EG, Takacs, CM, Ahmed, Y, Baird, JR, Benchabane, H	Development	2008
19619488	Wnt/beta-catenin signaling: components, mechanisms, and diseases MacDonald, BT, Tamai, K, He, X	Dev Cell	2009
15459103	Wnt signals across the plasma membrane to activate the beta-catenin pathway by forming oligomers containing its receptors, Frizzled and LRP Schweizer, L, Cong, F, Varmus, H	Development	2004
10647780	Modulation of Wnt signaling by Axin and Axil Kikuchi, A	Cytokine Growth Factor Rev.	1999
15084453	LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way Tamai, K, Zeng, X, Semenov, M, He, X	Development	2004
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
19759537	Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling Mickanin, C, Zhang, Y, Fawell, S, Mishina, YM, Fazal, A, Myer, V, Wiellette, E, Michaud, GA, Wiessner, S, Hild, M, Bauer, A, Porter, JA, Rau, C, Huang, SM, Lengauer, C, Finan, PM, Ghidelli, S, Serluca, F, Shao, W, Bouwmeester, T, Shi, X, Stegmeier, F, Shultz, M, Charlat, O, Kirschner, MW, Cong, F, Schirle, M, Schlegl, J, Curtis, D, Wilson, CJ, Tallarico, JA, Cheng, H, Cheung, A, Liu, S, Lu, C, Tomlinson, R	Nature	2009
14731402	A mechanism for Wnt coreceptor activation Zhang, X, Tamai, K, Chang, Z, Harada, Y, Zeng, X, He, X, Liu, C	Mol Cell	2004
10581160	A GSK3beta phosphorylation site in axin modulates interaction with beta-catenin and Tcf-mediated gene expression Lomvardas, S, Costantini, F, Jho, E	Biochem Biophys Res Commun	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
10421629	Wnt-induced dephosphorylation of axin releases beta-catenin from the axin complex Willert, K, Nusse, R, Shibamoto, S	Genes Dev	1999
22363759	Wnt signalling pathway parameters for mammalian cells Hirokawa, Y, Tan, CW, Layton, MJ, Burgess, AW, Smith, DW, Gardiner, BS	PLoS ONE	2012
16341017	A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation Tamai, K, Woodgett, J, Okamura, H, Doble, B, Li, S, Huang, H, Zeng, X, He, X, Habas, R	Nature	2005
14551908	The roles of APC and Axin derived from experimental and theoretical analysis of the Wnt pathway Kruger, R, Salic, A, Kirschner, MW, Lee, E, Heinrich, R	PLoS Biol	2003
11336703	Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway Li, L, Kimelman, D, Takada, S, Wu, D, Yuan, H, Farr GH, 3rd, Flynn, C, Pan, W, Liu, B, Wang, J, Mao, J	Mol Cell	2001