| Project/Area Number |
09044264
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Immunology
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| Research Institution | Institute of Molecular and Cellular Biosciences, The University of Tokyo |
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Principal Investigator |
MIYAJIMA Atsushi Institute of Molecular and Cellular Biosciences, The University of Tokyo, PROFESSOR, 分子細胞生物学研究所, 教授 (50135232)
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| Co-Investigator(Kenkyū-buntansha) |
COPELAND Neal National Cancer Institute, USA,Senior Risearcher, 主任研究員
JENKINS Nancy National Cancer Institute, USA,Senior Risearcher, 主任研究員
DAAR Ira National Cancer Institute, USA.Senior Risearcher, 主任研究員
DONOVAN Peter National Cancer Institute, USA,Senior Risearcher, 主任研究員
KINOSHITA Taisei Institute of Molecular and Cellular Biosciences, The University of Tokyo, ASSIST, 分子細胞生物学研究所, 助手 (40301113)
HARA Takahiko Institute of Molecular and Cellular Biosciences, The University of Tokyo, ASSOCI, 分子細胞生物学研究所, 助教授 (80280949)
NEAL Copelan 米国国立がん研究所, 主任研究員
NANCY Jenkin 米国国立がん研究所, 主任研究員
IRA Daar 米国国立がん研究所, 主任研究員
PETER Donova 米国国立がん研究所, 主任研究員
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 1998: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1997: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | cytokine / cytokine receptors / signal transduction / apoptosis / hematopoiesis / germ cells / endothelial cells / development / オンコスタチンM / 血管内皮 / セルトリ細胞 / 始原生殖細胞 / 細胞増殖 / 細胞分化 / 細胞死 / 白血病 |
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| Research Abstract |
Survival of hematopoietic cells depends on cytokine signals and cells undergo apoptosis upon cytokine depletion. As we have already demonstrated that RAS activated by cytokine stimulation is important for prevention of cell death, we analyzed signals downstream of RAS by using RAS mutants. We found that both RAF/MAP kinase and PI3 kinase activated by RAS are involved in suppression of cell death. In the absence of cytokines, caspase-3 is activated and is involved in induction of cell death. In addition, as we previously isolated Oncostatin M (OSM) as a cytokine-inducible gene, we searched for its biological activity. OSM was found to be expressed in the AGM region and was shown to have a profound effect on the development of hematopoietic cells as well as **dothelial cells, possibly acting on their common precursor cells, hemangioblasts. Using the in vitro culture system of the AGM region, role of c-myb and AML in hematopoiesis was studied. OSM was also found to be a growth factor of developing sertoli cells. The molecular structure of the OSM receptor was elucidated by cloning of the receptor cDNA.
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