| Project/Area Number |
10470087
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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 | Kumamoto University |
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Principal Investigator |
SAKAGUCHI Nobuo Kumamoto University, School of Medicine, Professor, 医学部, 教授 (70192086)
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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 |
¥10,200,000 (Direct Cost: ¥10,200,000)
Fiscal Year 1999: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1998: ¥5,300,000 (Direct Cost: ¥5,300,000)
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| Keywords | rapamycin / S6 kinase / mTor / protein synthesis pathway / Iga / MB-1 / B cell antigen receptor / gene knock out mice / 抗体産生 / CD40 / 抗原レセプター / 胚中心 / セントロサイト / モノクロナール抗体 / B細胞異常 / 抗体レパートリー |
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| Research Abstract |
We identified a novel phosphoprotein of BCR mediated signal transduction as a coprecipitated molecule with Iga (MB-1). The cDNA clone showed a unique structure and named it alpha4 as a fourth component associated with MB-1 protein. The yeast homologue (Tap42) was isolated by the other group and was found to be a critical molecule of the growth factor mediated signal transduction of rapamycin-sensitive pathway. The alpha4/Tap42 is now known as a major signal transduction molecule of rapamycin sensitive pathway leading to protein synthesis probably through the activation of S6 kinase activity.
We prepared the gene knock out mice and found that the alpha4 is essential for the growth especially at the embryonal development. By the conditional targeting strategy using Cre-lox P system we could delete the alpha4 locus on the X chromosome and show that alpha4 is also essential for the growth of mature B cells stimulated with BCR crosslinking. Here, we could clearly demonstrate that alpha4 is involved in the BCR-mediated signal transduction of rapamycin sensitivity for the protein synthesis. We will further study the biological function of alpha4 related pathway in the immune system.
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