Phosphorylation of β-Catenin by AKT Promotes β-Catenin Transcriptional Activity

Increased transcriptional activity of β -catenin resulting from Wnt/Wingless dependent or independent signaling has been detected in many types of human cancer, but the underlying mechanism of Wnt-independent regulation is poorly understood. We have demonstrated that AKT, which is activated downstream from EGFR signaling, phosphorylates β-catenin at Ser552 in vitro and in vivo. AKT-mediated phosphorylation of β -catenin causes its disassociation from cell-cell contacts and accumulation in both the cytosol and nucleus, and enhances its interaction with 14-3-3 ζ via a binding motif containing Ser552. Phosphorylation of β-catenin by AKT increases its transcriptional activity and promotes tumor cell invasion, indicating that AKT-dependent regulation of β-catenin plays a critical role in tumor invasion and development.