V-SRC KINASE SHIFTS THE CADHERIN-BASED CELL-ADHESION FROM THE STRONG TO THE WEAK STATE AND BETA-CATENIN IS NOT REQUIRED FOR THE SHIFT

The elevation of tyrosine phosphorylation level is thought to induce t he dysfunction of cadherin through the tyrosine phosphorylation of bet a catenin. We evaluated this assumption using two cell lines. First, u sing temperature-sensitive v-src-transfected MDCK cells, we analyzed t he modulation of cadherin-based cell adhesion by tyrosine phosphorylat ion. Cell aggregation and dissociation assays at nonpermissive and per missive temperatures indicated that elevation of the tyrosine phosphor ylation does not totally affect the cell adhesion ability of cadherin but shifts it from a strong to a weak state. The tyrosine phosphorylat ion levels of beta catenin, ZO-1, ERM (ezrin/radixin/moesin), but not alpha catenin, vinculin, and alpha-actinin, were elevated in the weak state. To evaluate the involvement of the tyrosine phosphorylation of beta catenin in this shift of cadherin-based cell adhesion, we introdu ced v-src kinase into L fibroblasts expressing the cadherin-alpha cate nin fusion protein, in which beta catenin is not involved in cell adhe sion. The introduction of v-src kinase in these cells shifted their ad hesion from a strong to a weak state. These findings indicated that th e tyrosine phosphorylation of beta catenin is not required for the str ong-to-weak state shift of cadherin-based cell adhesion, but that the tyrosine phosphorylation of other junctional proteins, ERM, ZO-1 or un identified proteins is involved.