Toggling a conformational switch in Wnt/[beta]-catenin signaling: Regulation of Axin phosphorylation

• Published in: BioEssays Vol. 35; no. 12; p. 1063
• Main Authors: Tacchelly-Benites, Ofelia, Wang, Zhenghan, Yang, Eungi, Lee, Ethan, Ahmed, Yashi
• Format: Journal Article
• Language: English
• Published: Cambridge Wiley Subscription Services, Inc 01.12.2013
• Subjects: Phosphorylation; Signal transduction
• ISSN: 0265-9247; 1521-1878
• DOI: 10.1002/bies.201300101

The precise orchestration of two opposing protein complexes - one in the cytoplasm ([beta]-catenin destruction complex) and the other at the plasma membrane (LRP6 signaling complex) - is critical for controlling levels of the transcriptional co-factor [beta]-catenin, and subsequent activation of the Wnt/[beta]-catenin signal transduction pathway. The Wnt pathway component Axin acts as an essential scaffold for the assembly of both complexes. How the [beta]-catenin destruction and LRP6 signaling complexes are modulated following Wnt stimulation remains controversial. A recent study in Science by He and coworkers reveals an underlying logic for Wnt pathway control in which Axin phosphorylation toggles a switch between the active and inactive states. This mini-review focuses on this and two other recent studies that provide insight into the initial signaling events triggered by Wnt exposure. We emphasize regulation of the [beta]-catenin destruction and LRP6 signaling complexes and propose a framework for future work in this area. [PUBLICATION ABSTRACT]