Uniaxial cyclic stretch induces focal adhesion kinase (FAK) tyrosine phosphorylation followed by mitogen-activated protein kinase (MAPK) activation

We investigated the role of tyrosine phosphorylation of FAK in the stretch- induced MAPKs (extracellular signal-regulated kinase (ERK), p38MAPK) activa tion in mutant FAK-transfected fibroblasts. In response to uniaxial cyclic stretch (1 Hz, 120% in length), the levels of tyrosine phosphorylation of t he Tyr-397 and Tyr-925 of FAK in control cells increased and peaked at 5 mi n (2.75 +/- 0.51, n = 3), and 20 min (2.98 +/- 0.58, n = 3), respectively, and the activities of MAPKs increased and peaked at approximately 10 min. O n the other hand, in the mutant FAK-transfected cells, the stretch-induced MAPKs activation was significantly inhibited. The stretch-induced activatio n of MAPKs was also significantly abolished by either treatment with Gd3+ o r extracellular Ca2+ removal which may inhibit intracellular Ca2+ increase caused by the activation of cation selective (Ca2+-permeable) stretch activ ated (SACatC) channels. These results suggest that the stretch-induced tyro sine-phosphorylation of FAK via SACatC activation is critical for the stret ch-induced MAPKs activation. (C) 2001 Academic Press.