2007 Fiscal Year Final Research Report Summary
A novel regulatory way of smooth muscle contraction
| Project/Area Number |
16209007
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Gunma University |
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Principal Investigator |
KOHAMA Kazuhiro Gunma University, Department of Molecular and Cellular Pharmacology, Professor (30101116)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIKAWA Ryoki Gunma University, Department of Molecular and Cellular Pharmacology, Assoc. Prof. (20212863)
NAKAMURA Akio Gunma University, Department of Molecular and Cellular Pharmacology, Assoc. Prof. (30282388)
YOSHIYAMA Shinji Gunma University, Department of Molecular and Cellular Pharmacology, Assist Prof. (30396650)
TANAKA Hideyuki Gunma University, Department of Faculty of Medicine, Research Associate (70343085)
NASU Ritsuko Takasaki University, Department of Health & Welfare Nutritia, Assist Prof. (60383147)
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| Project Period (FY) |
2004 – 2007
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| Keywords | Actin / Myosin / smooth muscle / Regulation / migration |
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| Research Abstract |
Myosin light-chain kinase (MLCK) of smooth muscle consists of an actin-binding domain at the N-terminal the catalytic domain in the central portion, and the myosin-binding domain at the C-terminal. The kinase activity is mediated by the catalytic domain that phosphorylates the myosin light-chain of 20 kDa (MLC20), activating smooth muscle myosin to interact with actin. Although the regulatory role of the kinase activity is well established, the role of non-kinase activity derived from actin-binding and myosin-binding domains remains unknown. We hypothesized that the actin-myosin interaction of smooth muscle could be activated by the non-kinase activity independently of MLC20 phosphorylation. We expressed cDNA of MLCK as a recombinant protein, and mutated it to lose the kinase activity, while keeping non-kinase activity unaffected. With the mutant, we detected an activating effect on the actin-myosin interaction. We also down-regulated MLCK expression by its RNAi in the cultured smooth muscle cells, to observe the lack of the activation. The rescue experiments with the MLCK-deficient cells demonstrated that MLC20 phosphorylation is not obligatory for the smooth muscle to contract.
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[Journal Article] Role of Non-kinase Activity of Myosin Light-chain Kinase in Regulating Smooth Muscle Contraction, a Review Dedicated to Dr. Setsuro Ebashi.2008
Author(s)
Nakamura A., Xie C., Zhang Y., Gao Y., Wang H-H., Ye L-H., Kishi H., Okagaki T., Ybshiyama S., Hayakawa K., Ishikawa R., Kohama K.
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Journal Title
Biochem. Biophys. Res. Commun. 369
Pages: 135-143
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Blebbistatin Inhibits the Chemotaxis of Vascular Smooth Muscle Cellsthrough Breaking the Interaction between Myosin II and Actin.2008
Author(s)
Wang H., Tanaka H., Qin X., Zhao T., Ye L., Okagaki T., Katayama T., Nakamura A., Ishikawa R., Thatcher S., Wright G., and Kohama K.
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Journal Title
J. Physiol. Heart Circ.Physiol. 294
Pages: H2060-H2068
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Role of Non-kinase Activity of Myosin Light- chain Kinase in Regulating Smooth Muscle Contraction, a Review Dedicated to Dr. Setsuro Ebashi2008
Author(s)
Nakamura A., Xie C., Zhang Y., Gao Y., Wang H-H., Ye L-H., Kishi H., Okagaki T., Yoshiyama S., Hayakawa K., Ishikawa R., Kohama K.
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Journal Title
Biochem. Biophys. Res. Commun 369
Pages: 135-143
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Blebbistatin Inhibits the Chemotaxis of Vascular Smooth Muscle Cells through Breaking the Interaction between Myosin II and Actin2008
Author(s)
Wang H., Tanaka H., Qin X., Zhao T., Ye L., Okagaki T., Katayama T., Nakamura A., Ishikawa R., Thatcher S., Wright G., and Kohama K.
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Journal Title
J. Physiol Heart Circ. Physiol 294
Pages: H2060-H2068
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Blebbistatin inhibits the chemotaxis of vascular smooth muscle cells through breaking the interaction between smooth muscle myosin II and actin2008
Author(s)
Wang H-H., Tanaka H., Qin X., Zhao T., Lihong Ye, Okagaki T., Katayama T., Nakamura A., Ishikawa R., Thatcher S.E., Wright G. L., and Kohama K.
Organizer
The Joint Biophysical Society 52nd Annual Meeting and 16th International Biophysics Congress
Place of Presentation
California
Year and Date
20080202-06
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Blebbistatin inhibits the chemotaxis of vascular smooth muscle cells through breaking the interaction between smooth muscle myosin II and actin.2008
Author(s)
Wang, H-H., Tanaka, H., Qin, X., Zhao, T., Lihong, Ye, Okagaki, T., Katayama, T., Nakamura, A., Ishikawa, R., Thatcher, S. E., Wright G. L., and Kohama, K.
Organizer
The Joint Biophysical Society 52nd Annual Meeting and 16th International Biophysics Congress
Place of Presentation
California
Year and Date
20080202-0206
Description
「研究成果報告書概要(和文)」より
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