ROCK isoform regulation of myosin phosphatase and contractility in vascular smooth muscle cells.
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.
Wang
Yuepeng
Y
Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, USA.
Zheng
Xiaoyu Rayne
XR
Riddick
Nadeene
N
Bryden
Meredith
M
Baur
Wendy
W
Zhang
Xin
X
Surks
Howard K
HK
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D048430:Cell Shape; D002478:Cells, Cultured; D006801:Humans; D007527:Isoenzymes; D008246:Lysophospholipids / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D032389:Myocytes, Smooth Muscle / Q000201:enzymology*; D018994:Myosin Light Chains / Q000378:metabolism*; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014661:Vasoconstriction; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*
D007527:Isoenzymes; D008246:Lysophospholipids; D018994:Myosin Light Chains; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C515851:ROCK1 protein, human; C515852:ROCK2 protein, human; D054460:rho-Associated Kinases; D043263:Myosin-Light-Chain Phosphatase; C032881:lysophosphatidic acid