1997 Fiscal Year Final Research Report Summary
The Function and Abnormality of myosin phosphatase in cardiovascular system
| Project/Area Number |
07457168
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | MIE UNIVERSITY |
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Principal Investigator |
NAKANO Takeshi Mie University, Department of First Internal Medicine, Professor, 医学部, 教授 (60111879)
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| Project Period (FY) |
1995 – 1997
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| Keywords | smooth muscle / myosin phosphorylation / myosin phosphatase / Rho-kinase / cariac muscle / phospholipids / A kinase / caradiomyopathy |
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| Research Abstract |
The function and abnormality of myosin phosphatase in cardiovascular system has been characterized in some detail and the following results have been presented.
1.Signal transduction mechanism through myosin phospnatase (MP) in smooth muscle Rho-kinase phosphorylated the regulatory subunit (MYPT) of MP and inactivated the holoenzyme in vitro. Constitutively active Rho-kinase can induce contraction in Triton-X-100-permeabilized smooth muscle of rabbit portal vein. This contraction was accompanied by proportional increases in monophosphorylated myosin light chain. From above results it seems that MP and Rho-kinase are the important factors responsible for the regulation of smooth muscle tone.
2.Identification of two human MYPT isoforms
We have identified two novel isoforms of MYPT of MP in human. MYPT1 isoform is quite similar to rat or chicken isoforms and show>80% sequence identity. MYPT1 is mainly located in various smooth muscle tissues. The gene of MYPT1 was found on chromosome 12 (12q15-q21.2). On the other hand, MYPT2 is found in heart and brain.and its gene was localized on chromosome 1 (1q32.1). Recent study shows that chromosome 1q32.1 contains the putative genes responsible for cardiomyopathy. Therefore we suggest that MYPT2 may be related to the occurrence of cardiomyopathy. With regard to this, further studies will be needed.
3.Interaction of MP and phospholipids
The interaction of MP with membrane components, i.e.various phospholipids was examined. The C-terminal part of MYPT was found to interact the acidic phospholipids. It was further shown that MYPT was phosphorylated by PKA and that phosphorylation of the MP holoenzyme decreased phospholipid binding with a recovery of phosphatase activity. These results support the idea that MP may interact with membranes and that phosphorylation by PKA could modify this interaction.
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[Publications] Takeshi Matsui, Mutsuki Amano, Takaharu Yamamoto, Kazuyasu Chihara, Masato Nakafuku, Masaaki Ito, Takeshi Nakano, Katsuya Okawa, Akihiro Iwamatsu and Kozo Kaibuchi: "Rhoassociated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho" EMBO J. 15. 2208-2216 (1996)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kazushi Kimura, Masaaki Ito, Mutsuki Amano, Kazuyasu Chihara, Yuko Fukata, Masato Nakafuku, Bunpei Yamamori, Jianhua Feng, Takeshi Nakano, Katsuya Okawa, Akihiro, Iwamatsu and Kozo Kaibuchi: "Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase)." Science. 273. 245-248 (1996)
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「研究成果報告書概要(欧文)」より
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[Publications] Masaaki Ito, Hiroyuki Shimizu, Masatoshi Miyahara, Jian-Hua Feng, Setsuya Okubo, Kazuhito Ichikawa, Tokuji Konishi, David J.Hartshorne and Takano: Smooth muscle myosin phospatatse. (Nakano, T.and Hartshorne D.J.ets). Splinger-Verlag, Tokyo, 187- (1995)
Description
「研究成果報告書概要(欧文)」より
