| Project/Area Number |
08839023
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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 |
免疫の制御機構
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| Research Institution | Tokyo Metropolitan Institute for Neuroscience |
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Principal Investigator |
OGIMOTO Mami Tokyo Metropolitan Institute for Neuroscience, Department of Microbiology & Immunology, Staff Scientist, 微生物学・免疫学研究部門, 主事 (80158609)
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| Co-Investigator(Kenkyū-buntansha) |
YAKURA Hidetaka Tokyo Metropolitan Institute for Neuroscience, Department of Microbiology & Immu, 微生物学・免疫学研究部門, 参事 (60166486)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | B-cell antigen receptor / CD45 / signal tranduction / growth arrest / JNK / p38 / ERK / B細胞 / アポトーシス / 増殖抑制 / MAPキナーゼファミリー / NF-κB |
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| Research Abstract |
We have been trying to elucidate the role of CD45 in B cell antigen receptor (BCR)-mediated signal transduction by using CD45-negative clones from immature and mature B cell lines. We previously reported that CD45 regulates various cellular processes in a distinct manner, depending on maturational stages of B cells. In an immature B cell line WEHI-231, BCR-mediated growth arrest and apoptosis are negatively regulated by CD45. In contrast, in a mature B cell line BAL-17, BCR-induced growth arrest is regulated positively and crucially by CD45.
To define more precisely the signal transduction pathways governed by CD45 in immature and mature B cells, we focused on MAP kinase pathways. The results demonstrated that in the immature B cell line WEHI-231, ERK kinase activity is regulated positively and JNK and p38 kinase activities are negatively regulated by CD45, whereas in the mature B cell line BAL-17, CD45 regulates ERK kinase negatively and JNK and p38 kinase activities positively. Thus, CD45 is concerned with regulation of different members of MAP kinase pathways in a discrete manner, and its regulatory mode in immature B cells is opposite to that in mature B cells. Furthermore, there was a close correlation between activation of JNK and p38 and an increase in the degree of growth arrest. We are in the process of examining the direct contribution of JNK and p38 to the growth arrest by using dominant negative form of MKK4 (an activator of JNK) and a p38 inhibitor (SB203580).
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