权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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.

已经证实，许多细胞外信号诱导受体连接的肌醇磷脂的周转，从而诱导钙动员和蛋白激酶C的激活。细胞表面受体向磷脂酶C传递信号的机制尚未阐明。在这项研究中，我们研究了GTP结合蛋白(G蛋白)在这些跨膜信号机制中的角色和作用。首先，我们对突触膜磷脂酶C进行了纯化和鉴定。我们还从包括大脑在内的多种组织中分离了多个MR值约为20.000的G蛋白(小分子MR G蛋白)，纯化并鉴定了除c-ki-ras和Rho蛋白外的两个新的G蛋白，命名为SMG p25A和SMG p21。有人认为ras蛋白可以修饰受体连接的磷脂酰肌醇的周转，我们目前正试图在一个无细胞的系统中，用膜磷脂酶C和细胞表面受体来重构这些ras和ras相关的小分子MR G蛋白。我们还用几个细胞系表征了生长因子受体连接的磷脂酰肌醇的周转。在NIH/3T3细胞和培养的平滑肌细胞中，蛙皮素和血管紧张素II通过将G蛋白解偶联到磷脂酶C来抑制由蛙皮素和血管紧张素II诱导的肌醇磷脂的水解。相反，在这两种细胞中，血小板衍生生长因子诱导的反应对蛋白激酶C不敏感。这些结果结合我们早期的观察结果表明，从受体到磷脂酶C有不同的信号通路。