ROCK isoform regulation of myosin phosphatase and contractility in vascular smooth muscle cells.
ROCK isoform regulation of myosin phosphatase and contractility in vascular smooth muscle cells.
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DOI：
10.1161/circresaha.108.188524
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发表时间：
2009-02-27
影响因子：
20.1
通讯作者：
Surks HK
中科院分区：
文献类型：
--
作者：
Wang Y;Zheng XR;Riddick N;Bryden M;Baur W;Zhang X;Surks HK
VSMC的异常收缩在血管疾病中起重要作用。RhoA/ROCK信号通路通过抑制肌球蛋白磷酸酶（MLCP）活性和增加肌球蛋白轻链（MLC）磷酸化来介导血管平滑肌收缩。两种ROCK亚型ROCK 1和ROCK 2在许多组织中表达，但ROCK 1和ROCK 2在血管平滑肌（VSM）中的亚型特异性作用以及ROCK介导的MLCP调节机制尚不清楚。在这项研究中，ROCK 2，而不是ROCK 1，直接结合到MLCP的肌球蛋白结合亚基（MBS），但两个ROCK亚型调节MLCP和MLC磷酸化。尽管ROCK 1和ROCK 2都调节MLCP，但ROCK亚型对VSMC形态有不同的相反作用，ROCK 2而不是ROCK 1在VSMC收缩性中起主导作用。这些数据支持虽然ROCK亚型通过不同的机制调节MLCP和MLC磷酸化，但它们在VSMC功能中具有不同的作用。
Abnormal VSMC contraction plays an important role in vascular diseases. The RhoA/ROCK signaling pathway is now well-recognized to mediate vascular smooth muscle contraction in response to vasoconstrictors by inhibiting myosin phosphatase (MLCP) activity and increasing myosin light chain (MLC) phosphorylation. Two ROCK isoforms, ROCK1 and ROCK2, are expressed in many tissues, yet the isoform specific roles of ROCK1 and ROCK2 in vascular smooth muscle (VSM) and the mechanism of ROCK-mediated regulation of MLCP are not well understood. In this study, ROCK2, but not ROCK1, bound directly to the myosin binding subunit (MBS) of MLCP, yet both ROCK isoforms regulated MLCP and MLC phosphorylation. Despite that both ROCK1 and ROCK2 regulated MLCP, the ROCK isoforms had distinct and opposing effects on VSMC morphology and ROCK2, but not ROCK1, had a predominant role in VSMC contractility. These data support that although the ROCK isoforms both regulate MLCP and MLC phosphorylation through different mechanisms, they have distinct roles in VSMC function.