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(Circulation Research. 2009;104:531.)
© 2009 American Heart Association, Inc.

Cellular Biology

ROCK Isoform Regulation of Myosin Phosphatase and Contractility in Vascular Smooth Muscle Cells

Yuepeng Wang, Xiaoyu Rayne Zheng, Nadeene Riddick, Meredith Bryden, Wendy Baur, Xin Zhang, Howard K. Surks

From the Molecular Cardiology Research Institute and the Department of Medicine, Division of Cardiology (Y.W., N.R., M.B., W.B., H.K.S.), Tufts Medical Center, Boston; and the Laboratory for Microsystems Technology (X.R.Z., X.Z.), Department of Manufacturing Engineering, Boston University, Mass.

Correspondence to Howard K. Surks, Molecular Cardiology Research Institute, Tufts Medical Center, Box 80, 800 Washington St, Boston, MA 02111. E-mail hsurks{at}tuftsmedicalcenter.org

Abnormal vascular smooth muscle cell (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 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 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 of MLCP, yet both ROCK isoforms regulated MLCP and myosin light chain 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 myosin light chain phosphorylation through different mechanisms, they have distinct roles in VSMC function.

Key Words: ROCK • myosin phosphatase • myosin light chain • myosin binding subunit

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