c-Abl Kinase Targets Tight Junction Protein ZO-2 in Regulation of Cell Migration and Morphology

c-Abl is a non-receptor tyrosine kinase involved in the regulation of cell migration and morphogenesis, but underlying mechanism remains unclear. Here, we report the identification of tight junction protein ZO-2 as a bona fide substrate of c-Abl. We show that c-Abl directly binds to and phosphorylates the C-terminus of ZO-2. In addition, c-Abl stimulates the activity of JAK1, which subsequently phosphorylates the N-terminus of ZO-2. Using the RNAi-mediated knockdown/rescue strategy, we demonstrate that c-Abl regulates cellular morphology and migration through targeting ZO-2 for phosphorylation. c-Abl activity is also associated with decreased traction forces exerted on the cell substrate and reduced monolayer tension, thus corroborating c-Abl kinase activity-mediated inhibition of cell migration. Collectively, our data uncover ZO-2 as a novel mediator for c-Abl-dependent regulation of cell migration.