Membrane depolarization-induced RhoA/Rho-associated kinase activation and sustained contraction of rat caudal arterial smooth muscle involves genistein-sensitive tyrosine phosphorylation
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- Mita Mitsuo
- Department of Pharmacodynamics, Meiji Pharmaceutical University, Japan
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- Tanaka Hitoshi
- Department of Pharmacodynamics, Meiji Pharmaceutical University, Japan
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- Yanagihara Hayato
- Department of Pharmacodynamics, Meiji Pharmaceutical University, Japan
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- Nakagawa Jun-ichi
- Department of Pharmacodynamics, Meiji Pharmaceutical University, Japan
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- Hishinuma Shigeru
- Department of Pharmacodynamics, Meiji Pharmaceutical University, Japan
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- Sutherland Cindy
- Smooth Muscle Research Group, Department of Biochemistry and Molecular Biology, University of Calgary, Canada
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- Walsh Michael P.
- Smooth Muscle Research Group, Department of Biochemistry and Molecular Biology, University of Calgary, Canada
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- Shoji Masaru
- Department of Pharmacodynamics, Meiji Pharmaceutical University, Japan
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Rho-associated kinase (ROK) activation plays an important role in K+-induced contraction of rat caudal arterial smooth muscle (Mita et al., Biochem J. 2002; 364: 431–40). The present study investigated a potential role for tyrosine kinase activity in K+-induced RhoA activation and contraction. The non-selective tyrosine kinase inhibitor genistein, but not the src family tyrosine kinase inhibitor PP2, inhibited K+-induced sustained contraction (IC50 = 11.3 ± 2.4 μM). Genistein (10 μM) inhibited the K+-induced increase in myosin light chain (LC20) phosphorylation without affecting the Ca2+ transient. The tyrosine phosphatase inhibitor vanadate induced contraction that was reversed by genistein (IC50 = 6.5 ± 2.3 μM) and the ROK inhibitor Y-27632 (IC50 = 0.27 ± 0.04 μM). Vanadate also increased LC20 phosphorylation in a genistein- and Y-27632-dependent manner. K+ stimulation induced translocation of RhoA to the membrane, which was inhibited by genistein. Phosphorylation of MYPT1 (myosin-targeting subunit of myosin light chain phosphatase) was significantly increased at Thr855 and Thr697 by K+ stimulation in a genistein- and Y-27632-sensitive manner. Finally, K+ stimulation induced genistein-sensitive tyrosine phosphorylation of proteins of ~55, 70 and 113 kDa. We conclude that a genistein-sensitive tyrosine kinase, activated by the membrane depolarization-induced increase in [Ca2+]i, is involved in the RhoA/ROK activation and sustained contraction induced by K+.<br>
収録刊行物
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- Journal of Smooth Muscle Research
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Journal of Smooth Muscle Research 49 (0), 26-45, 2013
日本平滑筋学会
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詳細情報 詳細情報について
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- CRID
- 1390282680034377728
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- NII論文ID
- 130004922368
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- ISSN
- 18848796
- 09168737
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- 本文言語コード
- en
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- データソース種別
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- JaLC
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- 使用不可