RPTP-α acts as a transducer of mechanical force on α(v)/β(3)-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 α(v)/β(3)-integrin–mediated cell–matrix connections requires the receptor-like tyrosine phosphatase α (RPTPα). RPTPα colocalizes with α(v)-integrins at the leading edge during early spreading, and coimmunoprecipitates with α(v)-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 α(v)/β(3)-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.