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Abstract

β-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 β-catenin. We show that CKII phosphorylates the N-terminal region of β-catenin and we identified Ser29, Thr102, and Thr112 as substrates for the enzyme. We provide evidence that CKII regulates the cytoplasmic stability of β-catenin and acts synergistically with GSK-3β in the multi-protein complex that controls the degradation of β-catenin. In comparing wild-type and Ser/Thr-mutant β-catenin, a decreased affinity of the mutant protein to α-catenin was observed. Moreover, kinase assays in vitro demonstrate a CKII-dependent increase in the binding of wild-type β-catenin with α-catenin. In line with that, cells expressing Ser/Thr-mutant β-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 β-catenin in the cadherin adhesion complex as well as its cytoplasmic stability.