| Project/Area Number |
10044238
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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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 | Chiba University, Graduate School of Medicine |
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Principal Investigator |
SAITO Takashi Chiba Univ., Grad. Sch. Of Med., Professor, 医学研究科, 教授 (50205655)
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| Co-Investigator(Kenkyū-buntansha) |
OHNO Hiroshi Kanazawa Univ., Cancer. Research Inst. Professor, がん研究所, 教授 (50233226)
ARASE Hisashi Chiba Univ., Grad. Sch. Of Med., Assistant, 医学研究科, 助手 (10261900)
MALISSEN Ber ルミニー免疫センター, 仏, センター長
BONIFACINO J NIH, NICHD・米国, 主任研究員
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 1999: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥4,100,000 (Direct Cost: ¥4,100,000)
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| Keywords | μ chain / ITAM / CTLA-4 / CD3ζ chain / AP-complex / intracellular protein trafficking / lymphocyte activation / tyrosine motif / CD3ζ鎖 / m鎖 / T細胞抗原レセプター / CD3複合体 / ノックアウトマウス / シグナル伝達 / アダプター複合体 / 細胞内蛋白輸送 / クラスリン被膜小胞 / チロシンシグナル |
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| Research Abstract |
Tyrosine signals are utilized in signal transduction and intracellular protein sorting. We analyzed function of tyrosine-based motif in both signaling and protein trafficking in immune system. We isolated the μ chain of AP-2 complex as a CTLA-4 binding molecule. The binding is dependent on tyrosine motif to which SHP-2 binds upon phosphorylation. Thus, single tyrosine regulates either endocytosis or signaling depending on its tyrosine phosphorylation. Two different μ chains, μ1 for lysosomal targeting and μ2 for endocytosis are known. We isolated new three μ chains, μ1B, μ3B and μ4. μ1B is expressed in epithelial cells-specific way and suggests an epithelial-specific transporting system. μ3B is specifically expressed in nerve system. We are making mice lacking these molecules. T cells are activated through ITAM of CD3 chains. Stimulation of T cells with antagonist peptide induced down-regulation of ζphosphorylation. Establishment and analysis of mice bearing ITAM-negative CD3ζ revealed that T cell function did not differ in the absence of ζ phosphorylation.
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