Tyrosine phosphorylation of p120ctn in v-Src transfected L cells depends on its association with E-cadherin and reduces adhesion activity

Cadherins are transmembrane glycoproteins involved in Ca²⁺-dependent cell-cell adhesion. Using L cells expressing one of three functional E-cadherin constructs, the wild-type, a chimeric molecule with α-catenin (EαC), and a tailless one, we determined the effect of v-Src expression on E-cadherinmediated adhesion. The aggregation of L cells expressing the wild-type or EαC chimeric protein, which both interact with p120^ctn, was reduced by v-Src expression, whereas that of L cells expressing the tail-less E-cadherin was not affected by the expression. Tyrosine phosphorylation of p120^ctn was observed in v-Src-transformed L cells expressing the wild-type or EαC chimeric protein, but not in ones expressing the tail-less E-cadherin. Thus, tyrosine phosphorylation of p120^ctn depends on the complex formation with E-cadherin and the resulting membrane localization. Constitutive phosphorylation of p120^ctn on serine and threonine residues also depends on the complex formation and membrane localization. Coexpression of the p120^ctn protein with an N-terminal deletion, which eliminates some potential tyrosine phosphorylation sites, or the protein with a single amino acid substitution (tyrosine at 217 to phenylalanine) resulted in an increase in the aggregation of v-Src-transformed EL and EαCL cells. These results indicate that tyrosine phosphorylation of p120^ctn is involved in the v-Src modulation of E-cadherin-mediated cell adhesion.