Rho-Rho kinase is involved in smooth muscle cell migration through myosin light chain phosphorylation-dependent and independent pathways
Rho-Rho kinase is involved in smooth muscle cell migration through myosin light chain phosphorylation-dependent and independent pathways
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DOI：
10.1016/s0021-9150(00)00585-2
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发表时间：
2001-04-01
期刊：
影响因子：
5.3
通讯作者：
Iguchi, A
中科院分区：
文献类型：
--
作者：
Ai, S;Kuzuya, M;Iguchi, A
虽然Rho，一个小的GT。Rho蛋白在平滑肌收缩和舒张中起重要作用，但Rho蛋白在平滑肌细胞迁移中的作用尚不清楚。本研究探讨Rho-Rho激酶通路在血小板源性生长因子（PDGF）和溶血磷脂酸（LPA）诱导的平滑肌细胞迁移中的作用。Rho特异性抑制剂C3转移酶可阻断PDGF和LPA诱导的SMC迁移。Y-27632是Rho激酶的直接靶分子，其特异性抑制剂，可浓度依赖性地抑制PDGF和LPA诱导的SMC迁移。虽然观察到用LPA处理的SMC中肌球蛋白轻链（MLC）磷酸化迅速增加，但没有检测到对PDGF的响应增强的MLC磷酸化。Y-27632抑制LPA诱导的以及基础水平的MLC磷酸化。ML-9肌球蛋白轻链激酶（MLCK）的特异性抑制剂，抑制PDGF和LPA诱导的SMC迁移，而不抑制MLC磷酸化，表明MLCK可能通过MLC磷酸化以外的机制促进SMC迁移。这些结果表明，Rho-Rho激酶通路参与SMC迁移，并且Rho-Rho激酶下游的不同信号通路可能参与LPA和PDGF诱导的SMC迁移。通过Rho-Rho激酶途径的MLC磷酸化似乎与LPA依赖性SMC迁移有关。而PDGF介导的SMC迁移不依赖于MLC磷酸化的增加，Rho-Rho激酶下游的其他靶分子似乎也参与其中。(C)2001爱思唯尔科学爱尔兰有限公司保留所有权利。
Although Rho, a small GTPase. has been demonstrated to play an important role in the smooth muscle contraction and relaxation, little is known about the involvement of Rho protein in smooth muscle cell (SMC) migration. In this study the role of Rho-Rho kinase pathway was examined in SMC migration induced by platelet-derived growth factor (PDGF) and lysophosphatidic acid (LPA). C3 transferase, a specific inhibitor of Rho, blocked SMC migration induced 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 chain (MLC) phosphorylation in SMC treated with LPA was observed, no enhanced MLC phosphorylation was detected in response to PDGF. Y-27632 suppressed LPA-induced as well as basal level of MLC phosphorylation. ML-9. a specific inhibitor of myosin light chain kinase (MLCK), inhibited PDGF and LPA-induced SMC migration without the suppression of MLC phosphorylation at 5 min incubation, 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 pathways 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 implicated 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 Science Ireland Ltd. All rights reserved.