Rho-Rho kinase is involved in smooth muscle cell migration through myosin light chain phosphorylation-dependent and independent pathways

Although Rho, a small GTPase. has been demonstrated to play an important ro le in the smooth muscle contraction and relaxation, little is known about t he involvement of Rho protein in smooth muscle cell (SMC) migration. In thi s study the role of Rho-Rho kinase pathway was examined in SMC migration in duced by platelet-derived growth factor (PDGF) and lysophosphatidic acid (L PA). C3 transferase, a specific inhibitor of Rho, blocked SMC migration ind uced by PDGF and LPA. Y-27632, a specific inhibitor of Rho kinase, a direct target molecule of Rho, inhibited PDGF and LPA-induced SMC migration in a concentration dependent manner. Although rapid increase in myosin light cha in (MLC) phosphorylation in SMC treated with LPA was observed, no enhanced MLC phosphorylation was detected in response to PDGF. Y-27632 suppressed LP A-induced as well as basal level of MLC phosphorylation. ML-9. a specific i nhibitor of myosin light chain kinase (MLCK), inhibited PDGF and LPA-induce d SMC migration without the suppression of MLC phosphorylation at 5 min inc ubation, suggesting that MLCK may contribute to SMC migration via mechanism other than MLC phosphorylation. These results suggest that Rho-Rho kinase pathway is implicated in SMC migration and that different signaling pathway s downstream of Rho-Rho kinase may be involved in LPA and PDGF-induced SMC migration. MLC phosphorylation via Rho-Rho kinase pathway appears to be imp licated in LPA-dependent SMC migration. Whereas PDGF-mediated SMC migration is independent of increased MLC phosphorylation and other target molecules downstream of Rho-Rho kinase seem to be involved. (C) 2001 Elsevier Scienc e Ireland Ltd. All rights reserved.