Protein kinase CKII regulates the interaction of beta-catenin with alpha-catenin and its protein stability

J Cell Sci. 2002 Dec 15;115(Pt 24):4743-53. doi: 10.1242/jcs.00154.

Abstract

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.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Casein Kinase II
  • Cell Line
  • Cytoplasm / metabolism
  • Cytoskeletal Proteins / chemistry
  • Cytoskeletal Proteins / metabolism*
  • DNA Primers
  • Humans
  • Immunohistochemistry
  • Mice
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Binding
  • Protein-Serine-Threonine Kinases / metabolism*
  • Sequence Homology, Amino Acid
  • Trans-Activators / chemistry
  • Trans-Activators / metabolism*
  • alpha Catenin
  • beta Catenin

Substances

  • CTNNA1 protein, human
  • CTNNB1 protein, human
  • CTNNB1 protein, mouse
  • Ctnna1 protein, mouse
  • Cytoskeletal Proteins
  • DNA Primers
  • Trans-Activators
  • alpha Catenin
  • beta Catenin
  • Casein Kinase II
  • Protein-Serine-Threonine Kinases