Wnt-induced dephosphorylation of Axin releases beta-catenin from the Axin complex

The stabilization of beta-catenin is a key regulatory step during cell fate changes and transformations to tumor cells. Several interacting proteins, including Axin, APC, and the protein kinase GSK-3 beta are implicated in re gulating beta-catenin phosphorylation and its subsequent degradation. Wnt s ignaling stabilizes beta-catenin, but it was not clear whether and how Wnt signaling regulates the beta-catenin complex. Here we show that Axin is dep hosphorylated in response to Wnt signaling. The dephosphorylated Axin binds beta-catenin less efficiently than the phosphorylated form. Thus, Wnt sign aling lowers Axin's affinity for beta-catenin, thereby disengaging beta-cat enin from the degradation machinery.