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Threonine 393 of β‐catenin regulates interaction with Axin
Author(s) -
Wu Hao,
Symes Karen,
Seldin David C.,
Dominguez Isabel
Publication year - 2009
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22260
Subject(s) - wnt signaling pathway , phosphorylation , xenopus , catenin , microbiology and biotechnology , threonine , mutant , beta catenin , biology , gsk 3 , kinase , chemistry , signal transduction , serine , biochemistry , gene
CK2 is a regulatory kinase implicated in embryonic development and in cancer. Among the CK2 substrates is β‐catenin, a protein with dual function in Wnt signaling and cell adhesion. Previously, we reported that CK2 activity is required for β‐catenin stability and we identified threonine (T) 393 as a major CK2 phosphorylation site in β‐catenin. However, it is not known whether phosphorylation at T393 increases β‐catenin stability and if so, what is the mechanism. In this study we investigate the molecular mechanism of β‐catenin stabilization through phosphorylation at T393. We found that pseudophosphorylation of β‐catenin at T393 resulted in a stable activated form of β‐catenin with decreased affinity for Axin in vitro. This phosphomimetic mutant also displayed decreased regulation by Axin in vivo in a bioassay in Xenopus laevis embryos. In contrast, the binding of T393 pseudophosphorylated β‐catenin to E‐cadherin was unaffected. Further analysis showed that pseudophosphorylation at T393 did not prevent β‐catenin phosphorylation by GSK3β. Interestingly, we found that in the presence of pseudophophorylated β‐catenin and another activated form of β‐catenin, the recruitment of GSK3β to Axin is enhanced. These findings indicate that phosphorylation of T393 by CK2 may affect the stability of β‐catenin through decreased binding to Axin. In addition, the increased recruitment of GSK3β to the destruction complex in the presence of activated β‐catenin mutants could be a feedback mechanism to suppress overactive Wnt signaling. J. Cell. Biochem. 108: 52–63, 2009. © 2009 Wiley‐Liss, Inc.