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

By D. Fang, D. Hawke, Yanhua Zheng, Yan Xia, J. Meisenhelder, H. Nika, Gordon B. Mills, Ryuji Kobayashi, T. Hunter, Zhimin Lu. Journal of Biological Chemistry, 2007

759 citations recorded by the source corpus.

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 epidermal growth factor receptor 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 the nucleus and enhances its interaction with 14-3-3ζ 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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/883d3591948adcb0ca9da360043a49de4f4b7b3c

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Citations in the corpus

Proteogenomic characterization reveals therapeutic vulnerabilities in lung adenocarcinoma (2020, background): “CTNNB1 has been shown to play a critical role in EGFR-driven LUAD (Nakayama et al., 2014), and the trans-regulated phosphosite S552 on CTNNB1 induces its transcriptional activity (Fang et al., 2007).”
Signal transduction in cancer. (2015, neutral): “…regulate proliferation, including those encoding Myc and cyclin D. Akt can also phosphorylate b-catenin directly, causing its dissociation from cadherin cell–cell adhesion complexes (see below), thus increasing the pool of b-catenin available and its transcriptional activity (Fang et al. 2007).”
Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration (2009, background): “Several biochemical interactions have been proposed for the relationship between PGE2 and wnt in vitro (Castellone et al., 2005; Fang et al., 2007; Fujino et al., 2002; Hino et al., 2005; Cell 136, 1136–1147, March 20, 2009 ª2009 Elsevier Inc. 1141 Shao et al., 2005).”
Wnt activity defines colon cancer stem cells and is regulated by the microenvironment (2010, background): “Moreover, a concomitant increase in phosphorylation of β-catenin on Ser 552, which is associated with enhanced transcriptio”
PKM2 Phosphorylates Histone H3 and Promotes Gene Transcription and Tumorigenesis (2012, neutral): “In Vitro Kinase Assays The kinase reactions were performed as described previously (Fang et al., 2007; Vander Heiden et al., 2010).”
The mammalian ovary from genesis to revelation. (2009, background): “For example, AKT directly phosphorylates -catenin, consequently increasing -catenin transcriptional activity and promoting tumor cell invasion in vitro (516).”