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 alpha(v)/beta(3)-integrin-mediated cell-matrix connections requires the receptorlike tyrosine phosphatase alpha (RPTPalpha). RPTPalpha colocalizes with alpha(v)-integrins at the leading edge during early spreading, and coimmunoprecipitates with alpha(v)-integrins during spreading on fibronectin and vitronectin. RPTPalpha-dependent activation of Src family kinases, in particular activation of Fyn, is required for the force-dependent formation of focal complexes and strengthening of alpha(v)/beta(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 RPTPalpha is an early component in force-dependent signal transduction pathways leading to the assembly of focal complexes on both fibronectin and vitronectin.