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

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-3 beta (GSK-3 beta) phosphorylation sites and is highly phosphorylated, Here we report that in vitro this region is indeed phosphorylated by CKII and GSK-3 beta, 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-3 beta appears to modulate the affinity between beta-catenin and E-cadherin, ultimately modifying the strength of cell-cell adhesion.