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

ABSTRACT c‐Abl is a non‐receptor tyrosine kinase involved in the regulation of cell migration and morphogenesis, but the 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, 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.