| Project/Area Number |
10557018
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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 | 展開研究 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Kobe University |
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Principal Investigator |
YAMAMURA Hirohei Kobe University School of Medicine, Professor, 医学部, 教授 (90030882)
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| Co-Investigator(Kenkyū-buntansha) |
TAKANO Tomoko Kobe University School of Medicine, Assistant Professor, 医学部, 助手 (30226807)
YANAGI Shigeru Kobe University School of Medicine, Associate Professor, 医学部, 助教授 (60252003)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 2000: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1999: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1998: ¥4,900,000 (Direct Cost: ¥4,900,000)
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| Keywords | Bacteria / Apoptosis / Protein-tyrosine kinase / Syk / Phospholipase D / B lymphocytes / Oxidative stress / Syk / 消去酵素 / アポトーシス / 放線菌 |
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| Research Abstract |
We have investigated the role of Syk protein-tyrosine kinase (PTK) in the intracellular signaling mechanism in variety of cells. In particular, our recent works have shown that PTKs play important roles in the regulatory mechanism of a B lymphocyte apoptosis mediated by the oxidative stress. On the other hand, we found that bacteria such as accidental actinomyces secreted unknown factor (s) which blocked apoptosis of B cells mediated by the oxidative stress. In this study, we have identified this factor as bacterial phospholipase D (PLD) which catalyzes phosphatidylcholine hydrolysis to choline and phosphatidic acid. Therefore, it is highly possible that phosphatidic acid blocked apoptosis of B cells mediated by the oxidative stress. To further understand the regulatory mechanism of PLD action on apoptosis signaling, we first examined the role and signaling pathway of endogenous PLD.We provide biochemical and genetic evidence that cross-linking of the B cell receptor (BCR) induces rapid activation of PLD through a Syk, Btk and phospholipase C (PLC)-gamma2 dependent pathway in DT40 B cells. In addition, we have shown that Syk, Btk and PLC-gamma2 pathway is required for phorbol ester-induced PLD activation in DT40 cells. Although we are now investigating the role of PLD action on apoptosis signaling, the exact molecular mechanism is still unknown. We are currently attempting to establish a PLD-deficient cell line by gene targeting in DT40 B cells. The genetic analysis of this mutant will provide a major tool in the physiological investigation of the functions of PLD.
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