Axin-dependent phosphorylation of the adenomatous polyposis coli protein mediated by casein kinase 1epsilon

J Biol Chem. 2001 Oct 19;276(42):39037-45. doi: 10.1074/jbc.M105148200. Epub 2001 Aug 3.

Abstract

Axin and the adenomatous polyposis coli protein (APC) interact to down-regulate the proto-oncogene beta-catenin. We show that transposition of an axin-binding site can confer beta-catenin regulatory activity to a fragment of APC normally lacking this activity. The fragment containing the axin-binding site also underwent hyperphosphorylation when coexpressed with axin. The phosphorylation did not require glycogen synthase kinase 3beta but instead required casein kinase 1epsilon, which bound directly to axin. Mutation of conserved serine residues in the beta-catenin regulatory motifs of APC interfered with both axin-dependent phosphorylation and phosphorylation by CKIepsilon and impaired the ability of APC to regulate beta-catenin. These results suggest that the axin-dependent phosphorylation of APC is mediated in part by CKIepsilon and is involved in the regulation of APC function.

MeSH terms

  • Adenomatous Polyposis Coli Protein / metabolism*
  • Amino Acid Sequence
  • Axin Protein
  • Binding Sites
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Casein Kinases
  • Cell Line
  • DNA, Complementary / metabolism
  • Down-Regulation
  • Gene Expression Regulation, Enzymologic
  • Genes, Reporter
  • Glycogen Synthase Kinase 3
  • Glycogen Synthase Kinases
  • Humans
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Mutation
  • Phosphorylation*
  • Protein Binding
  • Protein Kinases / metabolism*
  • Proteins / metabolism*
  • Repressor Proteins*
  • Serine / chemistry
  • Tumor Cells, Cultured

Substances

  • Adenomatous Polyposis Coli Protein
  • Axin Protein
  • DNA, Complementary
  • Proteins
  • Repressor Proteins
  • Serine
  • Protein Kinases
  • Glycogen Synthase Kinases
  • Casein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Glycogen Synthase Kinase 3