| Project/Area Number |
03671182
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Yamanashi Medical College |
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Principal Investigator |
OZAKI Yukio Yamanashi Medical College, Dept. of Clin. Lab. Med., Associate Professor, 医学部, 助教授 (30134539)
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| Co-Investigator(Kenkyū-buntansha) |
YATOMI Yutaka Yamanashi Medical College, Dept. of Clin. Lab. Med., Assistant, 医学部, 助手 (60200523)
陣内 由紀 山梨医科大学, 医学部, 医員
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1991: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Platelets / tyrosine Kinase / inositol phospholipid / PI(3,4)P2 / genistein / staurosporine / wheat germ agglutinin / イノシト-ルリン脂質 / 細胞内カルシウム動員 |
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| Research Abstract |
The effect of genistein, a tyrosine kinase inhibitor, was evaluated on platelet function. Genistein inhibited platelet intracellular calcium mobilization by lowering the production of inositol trisphosphate. The site of action was found to be at PI(4)P 5-kinase which catalyzes the formation of PI(4,5)P2. However, genistein appears to have no effect on tyrosine phosphorylation induced by thrombin, suggesting that the inhibitory effect of genistein on platelet calcium mobilization was independent of tyrosine phosphorylation. We screened for agents that suppress protein tyrosine phosphorylation induced by thrombin, and found that staurosporine, a protein kinase C inhibitor, was a potent inhibitor of tyrosine kinase. It inhibited the formation of PI(3,4)P2, suggesting that the tyrosine kinase activity is closely related to PI 3-kinase. Various aspects of platelet function induced by wheat germ agglutinin were almost completely inhibited by staurosporine, whereas specific protein kinase C inhibitors were without effect. These findings suggest that platelet activation induced by wheat germ agglutinin is closely related to tyrosine phosphorylation.
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