| Project/Area Number |
07409001
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
広領域
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| Research Institution | Institute of Molecular and Cellular Biosciencesa, 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) |
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)
若尾 宏 東京大学, 分子細胞生物学研究所, 助手 (10280950)
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| Project Period (FY) |
1995 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥36,500,000 (Direct Cost: ¥36,500,000)
Fiscal Year 1998: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1997: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1996: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1995: ¥24,000,000 (Direct Cost: ¥24,000,000)
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| Keywords | cytokine / cytokine receptors / signal transduction / hematopoiesis / differentiation / apoptosis / RAS / STAT / サイトカイン / サイトカイン受容体 / 血管内皮 / 発生 / 誘導遺伝子 / 細胞分化 / 造血因子 / JAK / Ras / 幹細胞 / 造血細胞 / 増殖 / 細胞死 / キナーゼ / 細胞増殖 |
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| Research Abstract |
As studies on signaling by using the mutant IL-3/GM-CSF/IL-5 receptors revealed two major signaling pathways, RAS and STAT5, we have focused our efforts to elucidate the role of these pathways in cytokine functions. Hematopoietic cells require cytokines for their growth and also for their survival. We found that activation of RAS is important for suppression of cell death. RAS activates both RAF/MAP kinase and P13 kinase and both pathways were found to be involved in suppression of cell death. We also showed that caspase-3 is involved in cell death induced by cytokine depletion in hematopoietic cells. To find the role of STAT5 in cytokine functions, we isolated STAT5 target genes. Among them, ClS encodes a novel SH2 protein that negatively regulates cytokine signaling. Expression of a dominant negative form of STAT5 blocked proliferation induced by IL-3 and erythroid differentiation induced by EPO, indicating that STAT5 plays a distinct role depending on the cell tynes. Cross talk between STAT5 and RAS was also demonstrated. In addition, we studied the function of Oncostatin M(OSM), another STAT5 target gene, and found that OSM plays an important role in development of hematopoietic cells and germ cells. The OSM receptor cDNA was cloned and the molecular structure of the functional receptor was elucidated.
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