| Project/Area Number |
62480452
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
物質生物化学
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| Research Institution | Kobe University |
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Principal Investigator |
TAKAI Yoshimi Kobe University, Faculty of Medicine, Professor, 医学部, 教授 (60093514)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASHITA Takayuki Kobe University, Faculty of Medicine, Research Associate, 医学部, 助手 (10166671)
KAIBUCHI Kozo Kobe University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (00169377)
KAWAHARA Yasuhiro Kobe University, Faculty of Medicine, Research Associate, 医学部, 助手 (80169755)
KIKUCHI Akira Kobe University, Faculty of Medicine, Research Associate, 医学部, 助手 (10204827)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1988: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1987: ¥4,200,000 (Direct Cost: ¥4,200,000)
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| Keywords | Phosphoinositide / Cell Surface Receptor / Phospholipase C / GTP-binding Protein / Protein Kinase C / 細胞増殖因子 / 受容体 / ジグリセリド / イノシトール三リン酸 |
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| Research Abstract |
It is well established that many extracellular signals elicit the receptor-linked phosphoinositide turnover and thereby induce both Ca^<2+> mobilization and protein kinase C activation. The mechanisms of signalling from the cell surface receptors to the phospholipase C have not been clarified. In this research project, we have investigated the roles and actions of GTP-binding proteins (G proteins) in these transmembrane signalling mechanisms. First, we have purified and characterized the synaptic membrane phospholipase C. We have also separated multiple G proteins with Mr values of about 20.000 (small Mr G proteins) from several tissues including cerebrum, purified and characterized two novel G proteins designated as smg p25A and smg p21, in addition to c-Ki-ras and rho proteins. It has been suggested that the ras protein modifies the receptor-linked phosphoinositide turnover, we are currently attempting to reconstitute these ras and ras-related small Mr G proteins with the membrane phospholipase C and cell surface receptors in a cell-free system. We have also characterized the growth factor receptor-linked phosphoinositide turnover using several cell lines. In NIH/3T3 cells and cultured smooth muscle cells, the bombesin-and angiotensin II-induced phosphoinositide hydrolysis is inhibited by protein kinase C by uncoupling the G protein to the phospholipase C. In contrast, the platelet derived-growth factor-induced reaction is insensitive to protein kinase C in both cell types. These results together with our earlier observations suggest that there are various signalling pathways from the receptors to the phospholipase C.
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