| Project/Area Number |
06404025
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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 |
Immunology
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| Research Institution | Tohoku University |
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Principal Investigator |
SUGAMURA Kazuo Tohoku University, School of Medicine, Professor, 医学部, 教授 (20117360)
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| Co-Investigator(Kenkyū-buntansha) |
KASAI Noriyuki Tohoku University, School of Medicine, Professor, 医学部, 教授 (60001947)
KONNO Tasuke Tohoku University, Institute of Development, Aging and Cancer, Professor, 加齢医学研究所, 教授 (00004846)
ASAO Hironobu Tohoku University, School of Medicine, Assistant Professor, 医学部, 助手 (80250744)
大保 和之 東北大学, 医学部, 助手 (70250751)
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| Project Period (FY) |
1994 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥32,900,000 (Direct Cost: ¥32,900,000)
Fiscal Year 1996: ¥8,100,000 (Direct Cost: ¥8,100,000)
Fiscal Year 1995: ¥9,700,000 (Direct Cost: ¥9,700,000)
Fiscal Year 1994: ¥15,100,000 (Direct Cost: ¥15,100,000)
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| Keywords | interleukin 2 (IL-2) / IL-2 receptor / cytokine / XSCID / T cell differntiation and growth / tyrosine kinase / knockout mice / インターロイキン2 (IL-2) / サイイトカイン / γ鎖ノックアウトマウス / IL-2 / γ鎖 / JAK1,3 / シグナル伝達 |
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| Research Abstract |
Human X-linked severe immunodeficiency (XSCID) is caused by mutations of the common cytokine receptor gamma chain (gammac chain) gene. In this research project, the functional significance of the gammac chain in interacellular signal transduction has been investigated. Consequently, it has been demonstrated that Jak3 tyrosine kinase is associated with the gammac chain, and Jakl is assicuated with the beta chain of IL-2 receptor and alpha chains of IL-4, IL-7 and IL-9 receptor via the box1 regions included in their cytoplasmic domains. Using box1 mutants of the IL-2 receptor beta chain, Jak1 was revealed to be dispensable for cell growth signal transduction mediated by IL-2, whereas Jak3 has been shown to be essential for such signal transduction. We have identified and molecularly cloned a novel signal transducing adaptor molecule named STAM.STAM was revealed to contain an SH3 domain and ITAM (Immunoreceptor tyrosine-based activation motif) region, which are essential for signal tansduction downstream of Jak3. We also generated mice lacking the gammac chain function caused by its mutation. The gammac chain-knockout mice should be a useful model for development of gene-therapy for human XSCID.
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