| Project/Area Number |
09044354
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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 | Tokyo Metropolitan Institute for Neuroscience |
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Principal Investigator |
YAKURA Hidetaka Tokyo Metropolitan Institute for Neuroscience, Department of Microbiology & Immunology, Director of Molecular research Division, 微生物学・免疫学研究部門, 参事 (60166486)
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| Co-Investigator(Kenkyū-buntansha) |
SCHRAVEN Burkhart Ruprecht-Karls University of Heidelberg Department of Immunology, Professor, 免疫学, 教授
KORETZKY Gary University of Iowa College of Medicine, Department of Internal Medicine, Profess, 医学部・内科学, 教授
MIZUNO Kazuya Tokyo Metropolitan Institute for Neuroscience, Department of Microbiology & Immu, 微生物学・免疫学研究部門, 副参事 (00219643)
KATAGIRI Tatsuo Tokyo Metropolitan Institute for Neuroscience, Department of Microbiology & Immu, 微生物学・免疫学研究部門, 主事 (00233742)
OGIMOTO Mami Tokyo Metropolitan Institute for Neuroscience, Department of Microbiology & Immu, 微生物学・免疫学研究部門, 主事 (80158609)
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| Project Period (FY) |
1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1997: ¥5,400,000 (Direct Cost: ¥5,400,000)
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| Keywords | tyrpsine phosphatase / signal transduction / lymphocyte / CD45 / PEP / MAP kinase |
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| Research Abstract |
This project was initiated to elucidate the function Of protein tyrosine phosphatases (PTPs) in B lymphocyte signaling. We focused on two PTPs : one is a receptor-type PTP,CD45, and the other is an intracellular PTP,PEP.In collaboration with Dr Denis Alexander, we demonstrated (1) that CD45 regulates BCR-induced Erk activation and JNK/p38 activation separately, (2) that regulation exerted by CD45 on Erk and JNK/p38 is opposite in immature and mature B cells, and (3) that JNK/p38 activities are correlated with enhanced BCR-induced growth arrest. These results suggest that CD45 regulates members of MAP kinase family differentially and the mode of regulation is distinct depending on the state of differentiation. We previously reported that tyrosine Phosphorylation of a protein Of 66 kDa is defective in CD45-deficient clones, implying that this protein may be a downstream target of CD45. Together with Dr Burkhart Schraven's group, we are in the process of characterizing the nature of a protein of 66 kDa using 2-D gel electrophoresis. Collaborative efforts with Dr Gary Koretzky's group showed that introduction of antisense PEP cDNA into WEHI-231 cells rescued almost completely BCR-induced growth arrest and apoptosis, suggesting that PEP is a positive and essential molecule for BCR signal transduction.
All these results, together with collaborators' work, were presented at the TMIN International Symposium organized by the head investigator and were published as the proceedings entitled "Kinases and Phosphatases in Lymphocyte and Neuronal Signaling" from Springer-Verlag.
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