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XB-ART-47207
Science May 17, 2013; 340 (6134): 867-70.

Wnt stabilization of β-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 .


Abstract
Wnt signaling stabilizes β-catenin through the LRP6 receptor signaling complex, which antagonizes the β-catenin destruction complex. The Axin scaffold and associated glycogen synthase kinase-3 (GSK3) have central roles in both assemblies, but the transduction mechanism from the receptor to the destruction complex is contentious. We report that Wnt signaling is governed by phosphorylation regulation of the Axin scaffolding function. Phosphorylation by GSK3 kept Axin activated ("open") for β-catenin interaction and poised for engagement of LRP6. Formation of the Wnt-induced LRP6-Axin signaling complex promoted Axin dephosphorylation by protein phosphatase-1 and inactivated ("closed") Axin through an intramolecular interaction. Inactivation of Axin diminished its association with β-catenin and LRP6, thereby inhibiting β-catenin phosphorylation and enabling activated LRP6 to selectively recruit active Axin for inactivation reiteratively. Our findings reveal mechanisms for scaffold regulation and morphogen signaling.

PubMed ID: 23579495
PMC ID: PMC3788643
Article link: Science
Grant support: [+]

Species referenced: Xenopus
Genes referenced: ctnnb1 gsk3b gys1 lrp6

References [+] :
Behrens, Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta. 1998, Pubmed, Xenbase