Protein tyrosine phosphatase activity is necessary for E-cadherin-activated Src signaling.

Co-operation between cadherin adhesion molecules and the cytoskeleton is a key aspect of tissue morphogenesis that is mediated by cortical signaling at adhesive junctions. One such signal is the non-receptor tyrosine kinase, Src, which acts in several pathways at epithelial junctions, including E-cadherin signaling itself. We now present two new insights into junctional Src signaling. Firstly, we report that upstream protein tyrosine phosphatase (PTP) activity is required to stimulate E-cadherin-activated Src signaling at junctions. Perturbing PTP activity with vanadate selectively reduced the activity of Src tyrosine kinases at junctions. Moreover, E-cadherin homophilic ligation could not stimulate Src signaling in vanadate-treated cells. Additionally, vanadate treatment phenocopied the effects of Src inhibition on the actin cytoskeleton, suggesting that PTP activity is required for the dynamic regulation of the actin cytoskeleton by cadherin-activated Src signaling. Secondly, we identified a role for PTP-activated Src signaling in supporting apical junctional tension by targeting non-muscle myosin IIB. The linear shape of the apical junctions was lost in PTP- and Src-inhibited cells, and inhibiting Src selectively affected the junctional localization of myosin IIB but not of myosin IIA. We conclude that PTP-activated Src signaling is a possible upstream regulator of myosin IIB at the epithelial zonula adherens.