Down-Regulation of Myosin Light Chain Kinase Expression in Vascular Smooth Muscle Cells Accelerates Cell Proliferation: Requirement of Its Actin-binding Domain for Reversion to Normal Rates

DOI Web Site PubMed 27 References
  • Wang Hong Hui
    Department of Molecular and Cellular Pharmacology, Gunma University Graduate School of Medicine, Japan Department of Molecular and Cellular Pharmacology, Gunma University Graduate School of Medicine, Japan
  • Nakamura Akio
    Department of Molecular and Cellular Pharmacology, Gunma University Graduate School of Medicine, Japan Department of Molecular and Cellular Pharmacology, Gunma University Graduate School of Medicine, Japan
  • Yoshiyama Shinji
    Department of Molecular and Cellular Pharmacology, Gunma University Graduate School of Medicine, Japan Department of Molecular and Cellular Pharmacology, Gunma University Graduate School of Medicine, Japan
  • Ishikawa Ryoki
    Department of Molecular and Cellular Pharmacology, Gunma University Graduate School of Medicine, Japan Department of Molecular and Cellular Pharmacology, Gunma University Graduate School of Medicine, Japan
  • Cai Na
    Department of Biochemistry, College of Life Sciences, Nankai University, P.R. China Department of Biochemistry, College of Life Sciences, Nankai University, P.R. China
  • Ye Li-Hong
    Department of Biochemistry, College of Life Sciences, Nankai University, P.R. China Department of Biochemistry, College of Life Sciences, Nankai University, P.R. China
  • Takano-Ohmuro Hiromi
    Research Institute of Pharmaceutical Sciences, Musashino University, Japan Research Institute of Pharmaceutical Sciences, Musashino University, Japan
  • Kohama Kazuhiro
    Department of Molecular and Cellular Pharmacology, Gunma University Graduate School of Medicine, Japan Research Institute of Pharmaceutical Sciences, Musashino University, Japan Department of Molecular and Cellular Pharmacology, Gunma University Graduate School of Medicine, Japan Research Institute of Pharmaceutical Sciences, Musashino University, Japan

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Abstract

Myosin light-chain kinase (MLCK) is a multi-domain protein with kinase and actin-binding domains, among others. Deficiency of MLCK expression in GBaSM-4 vascular smooth muscle cells enhanced cell proliferation rate and shortened cell doubling time. Transient transfection of the MLCK-deficient cells with cDNA constructs of either wild-type MLCK or its mutant lacking the kinase activity reverted the cell proliferation rate to that of wild-type cells, whereas that of MLCK lacking the actin-binding domain maintained cell proliferation at an elevated rate similar to the MLCK-deficient cells. Thus, the actin-binding domain of MLCK seems to play a role in regulating cell proliferation.

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