| Project/Area Number |
12670087
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Kobe University |
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Principal Investigator |
SHUNTOH Hisato Kobe University, School of Medicine, Associate Professor, 医学部, 助教授 (70206259)
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| Co-Investigator(Kenkyū-buntansha) |
KUNO Takayoshi Kobe University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (50144564)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | calcineurin / immunosuppressants / fission yeast / protein dephosphorylation / vesicular trafficking / cytokinesis / cell wall integrity / lipid kinase / 低分子量GTP結合タンパク質 / SIN / タンパク質脱燐酸化酵素 / 蛋白質リン酸化反応 / 免疫抑制薬 / GPIアンカー / イノシトールリン脂質 |
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| Research Abstract |
Calcineurin, a Ca^<2+>- and calmodulin-dependent protein phosphatase (protein phosphatase 2B), is a molecular target for the specific immunosuppressive drugs, such as cyclosporin A or FK506, used in organ transplantation. Calcineurin is enriched in the neural tissues, and also distributes broadly in other tissues. The structure of the protein is highly conserved from yeast to man.
We are studying calcineurin signal transduction pathway in the fission yeast Schizosaccharomyces pombe (S. pombe) because this system is amenable to genetics and has many advantages in terms of relevance to higher systems. To identify gene products sharing an essential function with calcineurin, we have screened for mutations that confer synthetic lethality with calcineurin deletion, and have identified ten complementation groups (its1〜10 for immunosuppressant and temperature-sensitive).
The combined use of powerful genetics and of specific calcineurin inhibitors in fission yeast identified new components of the calcineurin pathway, and defined new roles of calcineurin in the regulation of the many cellular processes. Recent our data have revealed functional interactions between calcineurin and PI signaling through Its5/PI4P 5 kinase. Calcineurin also paricipates in membrane traffic and septation initiation network (SIN) of fission yeast through its functional connection with the small GTPase Rab/Ypt family protein Its5/Ypt3, and Its10/Cdc7 protein kinase, respectively.
These findings provide further insight into the functional role of calcineurin-mediated signal transduction cascades.
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