1997 Fiscal Year Final Research Report Summary
Molecular mechanisms of PEST-domein tyrosine phosphatase PEP in B cells
| Project/Area Number |
08670379
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | 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) |
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) |
1996 – 1997
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| Keywords | tyrosine phosphatase / PEP / signal transduction / Crk / WEHI-231 / nuclear translocation / アポトーシス |
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| Research Abstract |
B cell antigen receptor (BCR)-initiated signaling is stringently controlled by protein kinases and phosphatases. In this study we examined the role of the intracellular protein tyrosine phosphatase PEP [proline-, glutamic acid-, serine-, and threonine-rich (PEST) domain phosphatase] expressed predominantly in hematopoietic cells. Western blot analysis revealed that BCR ligation significantly induces the nuclear expression of PEP in the immature WHEI-231 and the mature BAL-17 B cell lines. The nuclear induction of PEP seemed to be mediated by protein kinase C-dependent mechanisms.
To examine the direct contribution of PEP in BCR signaling, antisense PEP cDNA was transfected into WEHI-231 cells. Expression of PEP in two antisense transfectants was reduced 40-60%, and strikingly, anti-IgM-induced G1 arrest and apoptosis were almost completely rescued in these antisense clones. Taken collectively, these results suggest that the expression of PEP is required for the determination of B cell fate triggered by BCR engagement. Given that PEP binds to Csk, PEP may be involved in the regulation of Src-family tyrosine kinases. However, how PEP exerts its effect is not known in the nucleus where Csk is absent. We are in the process of identifying the PEP binding proteins and substrated in the nucleus to define the role of PEP in BCR signaling.
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[Publications] Yakura, H,Katagiri, T,Ogimoto, M,Hasegawa, K,Arimura, Y,Mitomo, K,and Mizuno, K: "Protein tyrosine phosphatases in B lymphocyte signal transduction." "Kinases and Phosphatases in Lymphocyte and Neuronal Signaling" (ed, Yakura, H). Springer-Verlag, Tokyo. 134-146 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Hasegawa, K,Katagiti, T,Ogimoto, M,Arimura, Y,Mizuno, K,Mitomo, K,and Yakura, H: "Role of PEST domain tyrosine phosphatase PEP in B cell antigen receptor-induced signaling." "Kinases and Phosphatases in Lymphocyte and Neuronal Signaling" (ed, Yakura, H). Springer-Verlag, Tokyo. 325-326 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Katagiri, T,Ogimoto, M,Hasegawa, K,Arimura, Y,Mitomo, K,Mizuno, K,Yakura, H: "CD45 differentially regulates B cell antigen receptor-mediated tyrosine phosphorylation in immature and mature B cells." "Kinases and Phosphatases in Lymphocyte and Neuronal Signaling" (ed, Yakura, H). Springer-Verlag, Tokyo. 328-329 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Ogimoto, M,Arimura, Y,Mitomo, K,Katagiri, T,Hasegawa, K,Mizuno, K,and Yakura, H: "Regulation of MAP kinases and NF-kappaB activation by CD45 in WEHI-231 and BAL-17 B cells" "Kinases and Phosphatases in Lymphocyte and Neuronal Signaling" (ed, Yakura, H). Springer-Verlag, Tokyo. 330-331 (1997)
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[Publications] Arimura, Y,Ogimoto, M,Mitomo, K,Katagiri, T,Hasegawa, K,Mizuno, K,and Yakura, H: "Role of CD45 in CD40 signaling inmature B lymphoma cells" "Kinases and Phosphatases in Lymphocyte and Neuronal Signaling" (ed, Yakura, H). Springer-Verlag, Tokyo. 334-335 (1997)
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「研究成果報告書概要(欧文)」より
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