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Reconstitution Of β-catenin Degradation In Xenopus Egg Extract
Published on: June 17, 2014
Phosphorylation of beta-catenin by AKT promotes beta-catenin transcriptional activity
Dexing Fang1, David Hawke, Yanhua Zheng
1Brain Tumor Center and Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Abstract:
Increased transcriptional activity of beta-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 epidermal growth factor receptor signaling, phosphorylates beta-catenin at Ser552 in vitro and in vivo. AKT-mediated phosphorylation of beta-catenin causes its disassociation from cell-cell contacts and accumulation in both the cytosol and the nucleus and enhances its interaction with 14-3-3zeta via a binding motif containing Ser552. Phosphorylation of beta-catenin by AKT increases its transcriptional activity and promotes tumor cell invasion, indicating that AKT-dependent regulation of beta-catenin plays a critical role in tumor invasion and development.
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