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Phosphoinositide metabolism in transmembrane signalling

跨膜信号传导中的磷酸肌醇代谢

基本信息

批准号：
62480452
负责人：
TAKAI Yoshimi
金额：
$ 3.97万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

项目摘要

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.

众所周知，许多细胞外信号引起受体连接的磷酸肌肽转换，从而诱导Ca^<2+>动员和蛋白激酶C激活。从细胞表面受体到磷脂酶C的信号传导机制尚未明确。在本研究项目中，我们研究了gtp结合蛋白（G蛋白）在这些跨膜信号传导机制中的作用和作用。首先，我们纯化并表征了突触膜磷脂酶c。我们还从包括大脑在内的几个组织中分离了多个Mr值约为20,000的G蛋白（小Mr G蛋白），除了c-Ki-ras和rho蛋白外，还纯化并表征了两个新的G蛋白，分别为smg p25A和smg p21。有人认为ras蛋白修饰了受体连接的磷酸肌肽的转换，我们目前正试图在无细胞系统中用膜磷脂酶C和细胞表面受体重建这些ras和ras相关的小Mr G蛋白。我们还利用几种细胞系描述了生长因子受体连接的磷酸肌肽转换。在NIH/3T3细胞和培养的平滑肌细胞中，蛋白激酶C通过将G蛋白与磷脂酶C解偶联来抑制bombesin-and angiotensin ii诱导的磷酸肌肽水解。相比之下，血小板衍生生长因子诱导的反应在两种细胞类型中对蛋白激酶C不敏感。这些结果与我们早期的观察结果一起表明，从受体到磷脂酶C有多种信号通路。