RPTP-α acts as a transducer of mechanical force on αv/β3-integrin–cytoskeleton linkages

Cell motility on ECM critically depends on the cellular response to force from the matrix. We find that force-dependent reinforcement of αv/β3-integrin–mediated cell–matrix connections requires the receptor-like tyrosine phosphatase α (RPTPα). RPTPα colocalizes with αv-integrins at the leading edge during early spreading, and coimmunoprecipitates with αv-integrins during spreading on fibronectin and vitronectin. RPTPα-dependent activation of Src family kinases, in particular activation of Fyn, is required for the force-dependent formation of focal complexes and strengthening of αv/β3-integrin–cytoskeleton connections during the initial phase of ECM contact. These observations indicate that Src family kinases have distinct functions during adhesion site assembly, and that RPTPα is an early component in force-dependent signal transduction pathways leading to the assembly of focal complexes on both fibronectin and vitronectin.