Toggling a conformational switch in Wnt/β-catenin signaling: regulation of Axin phosphorylation. The phosphorylation state of Axin controls its scaffold function in two Wnt pathway protein complexes

• Published in: BioEssays Vol. 35; no. 12; pp. 1063 - 1070
• Main Authors: Tacchelly-Benites, Ofelia, Wang, Zhenghan, Yang, Eungi, Lee, Ethan, Ahmed, Yashi
• Format: Journal Article
• Language: English
• Published: United States 01.12.2013
• Subjects: Animals; Axin Protein - metabolism; beta Catenin - genetics; beta Catenin - metabolism; Humans; Phosphorylation; Protein Binding; Signal Transduction; Wnt Signaling Pathway - genetics; Wnt Signaling Pathway - physiology; PP1; β-catenin destruction complex; Axin; Wnt signal transduction; LRP6 signaling complex
• ISSN: 0265-9247; 1521-1878
• DOI: 10.1002/bies.201300101

The precise orchestration of two opposing protein complexes - one in the cytoplasm (β-catenin destruction complex) and the other at the plasma membrane (LRP6 signaling complex) - is critical for controlling levels of the transcriptional co-factor β-catenin, and subsequent activation of the Wnt/β-catenin signal transduction pathway. The Wnt pathway component Axin acts as an essential scaffold for the assembly of both complexes. How the β-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 β-catenin destruction and LRP6 signaling complexes and propose a framework for future work in this area.