| 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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| Co-Investigator(Kenkyū-buntansha) |
伊藤 正明 三重大学, 医学部・附属病院, 講師 (00223181)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1996: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥3,900,000 (Direct Cost: ¥3,900,000)
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| Keywords | smooth muscle / myosin phosphorylation / myosin phosphatase / Rho-kinase / cariac muscle / phospholipids / A kinase / caradiomyopathy / ミオシンリン酸化 / 細胞接着 / ミオシンホルファラーゼ |
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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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