RIN1 regulates cell migration through RAB5 GTPases and ABL tyrosine kinases

Stimulation of a receptor tyrosine kinase (RT K), such as EGFR, leads to RA S activation followed by RIN1 activation. RIN1, in turn, activates RA B5 family GTPases, as well as ABL tyrosine kinases. As expected, RIN1 expression directly correlates with RA B5-mediated EGFR endocytosis. We previously showed that normal receptor endocytosis and internalized EGFR fate also depend on the ability of RIN1 to concomitantly activate ABL tyrosine kinases, consistent with the established role of ABL kinases in cytoskeleton remodeling and the growing evidence that such remodeling plays a role in endocytic processes. Here we report that growth factor-directed cell migration, a physiological process that involves receptor endocytosis and actin remodeling, also requires the ability of RIN1 to coordinate RA B5 GTPase and ABL tyrosine kinase pathways.