Protein kinase CKII regulates the interaction of β-catenin with α-catenin and its protein stability
Protein kinase CKII regulates the interaction of β-catenin with α-catenin and its protein stability
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DOI：
10.1242/jcs.00154
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发表时间：
2002-12-15
影响因子：
4
通讯作者：
Kemler, R
中科院分区：
文献类型：
--
作者：
Bek, S;Kemler, R
β-连环蛋白是一种多功能细胞组分，是几种蛋白激酶的底物。在这里，我们研究了蛋白激酶CKII（酪蛋白激酶II）和β-连环蛋白的相互作用。我们发现，CKII磷酸化的N-末端区域的β-连环蛋白，我们确定Ser 29，Thr 102，和Thr 112作为底物的酶。我们提供的证据表明，CKII调节β-连环蛋白的细胞质稳定性，并在控制β-连环蛋白降解的多蛋白复合物中与GSK-3 β协同作用。在比较野生型和Ser/Thr突变的β-连环蛋白时，观察到突变蛋白对α-连环蛋白的亲和力降低。此外，体外激酶测定证明了野生型β-连环蛋白与α-连环蛋白结合的CKII依赖性增加。与此一致，表达Ser/Thr突变型β-连环蛋白的细胞表现出增加的迁移潜力，这与增强的胞质定位和与突变蛋白的细胞骨架的减少的关联相关。从这些结果中，我们得出结论，CKII调节β-连环蛋白在钙粘蛋白粘附复合物的功能，以及其细胞质的稳定性。
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.