| Project/Area Number |
04670299
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | TOKYO METROPOLITAN INSTITUTE FOR NEUROSCIENCES |
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Principal Investigator |
YAKURA Hidetaka Tokyo Metropolitan Institute for Neuroscience, Department of Microbiology and Immunology, Director, 微生物学・免疫学研究部門, 副参事研究員 (60166486)
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| Co-Investigator(Kenkyū-buntansha) |
KATAGIRI Tatsuo Tokyo Metropolitan Institute for Neuroscience, Department of Microbiology & Immu, 微生物学・免疫学, 主任研究員 (00233742)
OGIMOTO Mami Tokyo Metropolitan Institute for Neuroscience, Department of Microbiology & Immu, 微生物学・免疫学, 主任研究員 (80158609)
MIZUNO Kazuya Tokyo Metropolitan Institute for Neuroscience, Department of Microbiology & Immu, 微生物学・免疫学, 主任研究員 (00219643)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Tyrosine phosphatase / CD45 / B cell / Central nervous system / signal transduction / MPTP-delta / Apoptosis / MPTPdelta / HPTPdelta / レセプター型チロシンフォスファターゼ / B細胞活性化 / MRPTP / HPTP / アイソフォーム・スイッチ |
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| Research Abstract |
Cell activation, proliferation, and differentiation are regulated by protein tyrosine phosphorylation. This process is strictly controlled by interplays between protein tyrosine kinases (PTKs) and protein tyrosin phosphatases (PTPs). In this project, we tried to resolve the mechanisms underlying the B cell activation and inactivation by analyzing the function of CD45, a prototypic PTP, and to gain some insights into the regulation of the central nervous system by identifying PTPgenes expressed in the brain. The followings are the results obtained from the studies of the last two years :
1. Differential regulation of B cell activation and inactivation by CD45
CD45-negative clones were established from an immature B cell line and a mature B cell line, and the functional properties of the CDE45-negative clones were compared with the parental cells. The results demonstrated that CD45 on immarture B cells negatively regulates antigen receptor-mediated signaling whereas in mature B cells, CD45 an indispensable positive regulatory molecule.
2. Regulation of CD45 PTP activity by the extracdellular domain
Changes in the PTP activity after binding of native CD45 with various CD45 monoclonal antibodies were measured. In the event, only one monoclonal antibody aginst a common epitope down-regulated the PTP activity, suggesting that the CD45 PTP activity is regulated by structural perturbations in specific regions of the extracellular domain.
3. Identification of PTPs expressed in the immune and the central nervous sytems
We isolated MPTP delta gene from mouse brain cDNA library. The cytoplasmic domain contained two tandem repeats of PTP domain and the extracellular domain was composed of Ig-like and fibronectin type III-like domains. MPTP delta mRNA was expressed in specialized regions of the brain and lymphoid cells. Futher, its expression was developmentally controlled both in the brain and in thymus.
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