Protein kinase CKII regulates the interaction of β-catenin with α-catenin and its protein stability

被引:73
作者
Bek, S [1 ]
Kemler, R [1 ]
机构
[1] Max Planck Inst Immunobiol, Dept Mol Embryol, Stuebeweg 51, D-79108 Freiburg, Germany
关键词
casein kinase II; beta-catenin; alpha-catenin; protein kinase; caderin adhesion complex;
D O I
10.1242/jcs.00154
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
beta-Catenin is a multi-functional cellular component and a substrate for several protein kinases. Here we investigated the interaction of protein kinase CKII (casein kinase II) and beta-catenin. We show that CKII phosphorylates the N-terminal region of beta-catenin and we identified Ser29, Thr102, and Thr112 as substrates for the enzyme. We provide evidence that CKII regulates the cytoplasmic stability of beta-catenin and acts synergistically with GSK-3beta in the multi-protein complex that controls the degradation of beta-catenin. In comparing wild-type and Ser/Thr-mutant beta-catenin, a decreased affinity of the mutant protein to alpha-catenin was observed. Moreover, kinase assays in vitro demonstrate a CKII-dependent increase in the binding of wild-type beta-catenin with alpha-catenin. In line with that, cells expressing Ser/Thr-mutant beta-catenin exhibit an increased migratory potential, which correlates with an enhanced cytosolic localization and a reduced association with the cytoskeleton of the mutant protein. From these results we conclude that CKII regulates the function of beta-catenin in the cadherin adhesion complex as well as its cytoplasmic stability.
引用
收藏
页码:4743 / 4753
页数:11
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