Wnt stabilization of β-catenin reveals principles for morphogen receptor-scaffold assemblies

Sung Eun Kim, He Huang, Ming Zhao, Xinjun Zhang, Aili Zhang, Mikhail V. Semonov, Bryan T. MacDonald, Xiaowu Zhang, Jose Garcia Abreu, Leilei Peng, Xi He

Research output: Contribution to journalArticle

143 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)867-870
Number of pages4
JournalScience
Volume340
Issue number6134
DOIs
StatePublished - May 17 2013

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Wnt stabilization of β-catenin reveals principles for morphogen receptor-scaffold assemblies'. Together they form a unique fingerprint.

  • Cite this

    Kim, S. E., Huang, H., Zhao, M., Zhang, X., Zhang, A., Semonov, M. V., MacDonald, B. T., Zhang, X., Abreu, J. G., Peng, L., & He, X. (2013). Wnt stabilization of β-catenin reveals principles for morphogen receptor-scaffold assemblies. Science, 340(6134), 867-870. https://doi.org/10.1126/science.1232389