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

具有GTPase活性的RAS P21/RAS样小GTP结合蛋白（小G蛋白）的超家族。据报道，已有40多名成员，所有成员的MRS在20,000至41,000之间都是由单个特异性多肽组成的。有证据表明，小的G蛋白参与细胞内允许系统。在该研究项目中，我们研究了翻译后修饰，激活模式和小G蛋白的功能。大多数小的G蛋白具有至少一个半胱氨酸居住的独特共识C末端基序。我们发现，SMG P21b，RhoA P21和SMG P25A的C末端半胱氨酸保留是Geranygeranylation的，并且这些蛋白质对于每个小G蛋白与膜结合至关重要。小的G蛋白具有两种可互通的形式，GDP结合和GTP结合的活性形式。 GD分别从GDP结合到GTP结合形式和反向转换的转换分别诱导……更多的P/GTP交换和GTPase反应。我们已经纯化并表征了几种GDP/GTP交换蛋白（GDP解离刺激剂（GDS）和GDP解离抑制剂（GDI））和GTPase激活蛋白（GAP）的小G蛋白。 GDS和GDI还调节小G蛋白与膜的结合。 GTP结合的小G蛋白与其特定效应子蛋白蛋白相互作用并执行其特定作用。 SMG P21B与RAS P21间隙相互作用，并抑制RAS P21的RAS P21间隙活性。由于SMG P21B被蛋白激酶A磷酸化，因此可以想象SMG P 21B存在于蛋白激酶A的下流流中。我们还发现，在调节的秘密细胞中检测到SMG P25A，但在宪法秘密细胞中未检测到SMG P25A。由于在大多数受调节的秘密细胞中，蛋白激酶C的激活刺激了蛋白质C和CA^<2+>动员，因此SMG P25a可能存在于蛋白激酶C和Ca^<2+>的下降流中。这些结果表明，小的G蛋白及其调节蛋白受到众所周知的细胞内允许系统的调节，并构成了巨大的网络，用于细胞内调节机制。较少的