Casein kinase II phosphorylation of E-cadherin increases E-cadherin/beta-catenin interaction and strengthens cell-cell adhesion

J Biol Chem. 2000 Feb 18;275(7):5090-5. doi: 10.1074/jbc.275.7.5090.

Abstract

Beta-catenin, a member of the Armadillo repeat protein family, binds directly to the cytoplasmic domain of E-cadherin, linking it via alpha-catenin to the actin cytoskeleton. A 30-amino acid region within the cytoplasmic domain of E-cadherin, conserved among all classical cadherins, has been shown to be essential for beta-catenin binding. This region harbors several putative casein kinase II (CKII) and glycogen synthase kinase-3beta (GSK-3beta) phosphorylation sites and is highly phosphorylated. Here we report that in vitro this region is indeed phosphorylated by CKII and GSK-3beta, which results in an increased binding of beta-catenin to E-cadherin. Additionally, in mouse NIH3T3 fibroblasts expression of E-cadherin with mutations in putative CKII sites resulted in reduced cell-cell contacts. Thus, phosphorylation of the E-cadherin cytoplasmic domain by CKII and GSK-3beta appears to modulate the affinity between beta-catenin and E-cadherin, ultimately modifying the strength of cell-cell adhesion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Base Sequence
  • Cadherins / metabolism*
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Casein Kinase II
  • Cell Adhesion*
  • Cytoplasm / enzymology
  • Cytoplasm / metabolism
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • DNA Primers
  • Glycogen Synthase Kinase 3
  • Glycogen Synthase Kinases
  • Mice
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Protein Binding
  • Protein-Serine-Threonine Kinases / metabolism*
  • Recombinant Proteins / metabolism
  • Trans-Activators*
  • beta Catenin

Substances

  • CTNNB1 protein, mouse
  • Cadherins
  • Cytoskeletal Proteins
  • DNA Primers
  • Recombinant Proteins
  • Trans-Activators
  • beta Catenin
  • Glycogen Synthase Kinases
  • Casein Kinase II
  • Protein-Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Glycogen Synthase Kinase 3