| Project/Area Number |
14580698
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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 |
Cell biology
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| Research Institution | Kinki University (2004)
Kobe University (2002-2003) |
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Principal Investigator |
SUGIURA Reiko Kinki University, School of Pharmaceutical Sciences, Professor, 薬学部, 教授 (90294206)
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| Co-Investigator(Kenkyū-buntansha) |
KUNO Takayoshi Kobe University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (50144564)
SHUNTOH Hisato Kobe Gakuin University, Faculty of rehabilitation, Professor, 医療福祉学部, 教授 (70206259)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | immunosuppressant / fission yeast / phosphorylation / cytokinesis / membrane trafficking / RNA-binding protein / MAP kinase / タンパク質脱リン酸化 / 分子遺伝学 / 変異体 / ゲノム薬理学 / カルシニューリン / マップキナーゼ / 分裂酵母モデル系 / 転写因子 / カルシウムシグナル / 低分子量GTP結合蛋白質 / 免疫抑制薬FK506 / 蛋白質脱リン酸化 / シグナル伝達 |
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| Research Abstract |
Calcineurin (protein phosphatase 2B), the only serine/threonine phosphatase under the control of Ca2+/calmodulin, is an important mediator in signal transmission, connecting the Ca2+-dependent signalling to a wide variety of cellular responses. Calcineurin is an in vivo target of the immunosuppressant drug FK506 in fission yeast, and inhibition of calcineurin activity by gene disruption or by the addition of FK506 to the media does not affect the vegetative growth of fission yeast. We performed a genetic screen to search for the mutations that show sensitivity to the immunosuppressive drug FK506, and identified eight complementation groups. We identified PI4P5K Ypt3 small GTPase, subunits of clathrin-adaptor complex and demonstrated that these molecules and calcineurin share an essential function in cellular events such as cytokinesis, cell integrity and membrane trafficking. We also identified a downstream target of calcinerin ; Prz1, a zinc finger-type transcription factor. Prz1 was shown to be dephosphorylated by calcineurin and its transcriptional activity was also under the control of calcineurin-mediated signalling. Another approach to identify molecules that functionally interact with calcineurin signalling utilizes our discovery that calcineurin and the Pmk1 MAPK signalling function antagonistically in the Cl- homeostasis of fission yeast. Using this approach, we identified pmp1+ encoding MAPK phosphatase, pek1+ encoding MAPK kinase, and rnc1+, encoding an RNA-bindign protein. We also demonstrated that Pmp1 dephosphorylates and inactivates Pmk1, thereby negatively regulates Pmk1 siganlling. Rnc1 is a KH-type RNA-binding protein that binds and stabilizes the Pmp1 mRNA, thus acting as a negative feedback regulator of MAPK signalling.
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