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Small GTP-Binding Proteins and Intracellular Messenger Systems

小 GTP 结合蛋白和细胞内信使系统

基本信息

批准号：
01480529
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：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01480529/
关键词：
Small GTP-Binding Protein Intracellular Messenger Systems Prenylation GDP GTP Exchange Protein GTPase Activating Protein ゲニラルゲラニル基 GTP結合蛋白質 smgp21 smgp25A GAP GDI

项目摘要

There is a superfamily of ras p21/ras p21-like small GTP-binding proteins (small G proteins) with GTPase activity. Over forty members have been reported, and all of them with Mrs between 20,000 and 41,000 are composed of a single respective polypeptide. Evidence is accumulating that small G proteins are involved in intracellular messenger systems. In this research project, We have investigated the postーtranslational modifications, the modes of activation and the functions of small G proteins. Most of small G proteins have the unique consensus C-terminal motifs containing at least one cysteine residue. We have found that the C-terminal cysteine residues of smg p21B, rhoA p21 and smg p25A are geranygeranylated and that these prenylations are essential for each small G protein to bind to membranes. Small G proteins have two interconvertible forms, GDP-bound inactive and GTP-bound active forms. The conversion from the GDP-bound to GTP-bound form and the reverse conversion are induced by GD … More P/GTP exchange and GTPase reactions, respectively. We have purified and characterized several GDP/GTP exchange proteins (GDP dissociation stimulator (GDS) and GDP Dissociation inhibitor (GDI) ) and GTPase activating Proteins (GAP) for small G Proteins. GDS and GDI also regulate the binding of small G proteins to membranes. The GTP-bound form small G proteins interact with their specific effector proteins proteins and exert their specific actions. Smg p21B interacts with ras p21 GAP and inhibits the ras p21 GAP activity for ras p21. Since smg p21B is phosphorylated by protein kinase A, it is conceivable that smg p 21B is present in the down stream of protein kinase A. We have also found that smg p25A is detected in regulated secretory cells but not in constitutive secretory cells. Since in most of regulated secretory cells secretion is stimulated by the activation of protein kinase C and the Ca^<2+> mobilization, smg p25A might be present in the down stream of protein kinase C and Ca^<2+>. These results suggest that small G proteins and their regulatory proteins are regulat ed by well-known intracellular messenger systems and constitute a huge network with them for intracellular regulatory mechanisms. Less

存在具有GTP酶活性的ras p21/ras p21样小GTP结合蛋白（小G蛋白）超家族。据报道，已有超过四十个成员，并且所有Mrs在20，000到41，000之间的成员都由单一的相应多肽组成。越来越多的证据表明，小G蛋白参与细胞内信使系统。本课题研究了小G蛋白的翻译后修饰、激活方式和功能。大多数小G蛋白都具有独特的C-末端保守基序，其中至少含有一个半胱氨酸残基。我们已经发现，smg p21 B，rhoA p21和smg p25 A的C-末端半胱氨酸残基是geranygeranylated，这些prenylation是必不可少的每个小G蛋白结合膜。小G蛋白有两种相互转化的形式，GDP结合的非活性形式和GTP结合的活性形式。GD诱导了从GDP结合型到GTP结合型的转化和反向转化 ...更多信息 P/GTP交换和GTP酶反应。我们已经纯化并鉴定了几种GDP/GTP交换蛋白（GDP解离刺激物（GDS）和GDP解离抑制物（GDI））和小G蛋白的GTP酶激活蛋白（GAP）。GDS和GDI还调节小G蛋白与膜的结合。GTP结合型小G蛋白与其特异性效应蛋白相互作用，发挥其特异性作用。Smg p21 B与ras p21 GAP相互作用并抑制ras p21的ras p21 GAP活性。由于smg p21 B被蛋白激酶A磷酸化，因此可以认为smg p21 B存在于蛋白激酶A的下游。我们还发现，smg p25 A被检测到的调节分泌细胞，但不是在组成性分泌细胞。由于在大多数受调节的分泌细胞中，蛋白激酶C的激活和Ca^2+的动员刺激分泌，因此smg p25 A可能存在于蛋白激酶C和Ca^2+的下游。这些结果表明，小G蛋白及其调控蛋白受已知的细胞内信使系统的艾德，并与它们构成一个巨大的细胞内调控网络。少