Small GTP-Binding Proteins and Intracellular Messenger Systems

小 GTP 结合蛋白和细胞内信使系统

• 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

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

存在一个具有 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，有四十多个成员，Mrs 数在 20,000 到 41,000 之间的所有成员都由单一的各自的多肽组成。越来越多的证据表明，小 G 蛋白参与细胞内信使系统。在这个研究项目中，我们研究了小G蛋白的翻译后修饰、激活模式和功能。大多数小 G 蛋白具有独特的共有 C 端基序，其中包含至少一个半胱氨酸残基。我们发现smg p21B、rhoA p21 和smg p25A 的C 端半胱氨酸残基被香叶香叶基化，并且这些异戊二烯化对于每个小G 蛋白与膜的结合是必需的。小 G 蛋白有两种可相互转化的形式：GDP 结合的非活性形式和 GTP 结合的活性形式。从 GDP 结合形式到 GTP 结合形式的转化以及反向转化分别由 GD … More P/GTP 交换和 GTPase 反应诱导。我们纯化并表征了几种 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结合形式的小G蛋白与其特定的效应蛋白相互作用并发挥其特定的作用。 Smg p21B 与 ras p21 GAP 相互作用并抑制 ras p21 的 ras p21 GAP 活性。由于smg p21B被蛋白激酶A磷酸化，因此可以想象smg p21B存在于蛋白激酶A的下游。我们还发现smg p25A在调节性分泌细胞中检测到，但在组成性分泌细胞中未检测到。由于在大多数受调节的分泌细胞中，分泌是通过蛋白激酶C的激活和Ca 2+ 动员来刺激的，因此smg p25A可能存在于蛋白激酶C和Ca 2+ 的下游。这些结果表明，小G蛋白及其调节蛋白受到众所周知的细胞内信使系统的调节，并与它们构成了细胞内调节机制的巨大网络。较少的

项目成果

Fukumoto,Y.: "Activation of the cーfos serumーresponse element by the activated cーHaーras protein in a manner independent of protein kinase C and cAMPーdependent protein kinase." J.Biol.Chem.265. 774-780 (1990)

Fukumoto, Y.：“激活的 c-Haras 蛋白以独立于蛋白激酶 C 和 cAMP 依赖性蛋白激酶的方式激活 c-fos 血清反应元件。”J.Biol.Chem.265。 (1990)

Kawata, M.: "Identification of a Major GTP-Binding Protein in Bovine Aortic Smooth Muscle Membranes as smg p21, a GTP-Binding Protein Having the Same Effector Domain." Biochem. Biophys. Res. Commun.163. 1418-1427 (1989)

Kawata, M.：“牛主动脉平滑肌膜中主要 GTP 结合蛋白的鉴定为 smg p21，一种具有相同效应器结构域的 GTP 结合蛋白。”

Isomura, M.: "Partial Purification and Characterization of GDP Dissociation Stimulator (GDS)for the rho Proteins Bovine Brain Cytosol." Biochem. Biophys. Res. Commun.169. 652-659 (1990)

Isomura, M.：“rho 蛋白牛脑细胞质的 GDP 解离刺激物 (GDS) 的部分纯化和表征。”

Hiroyoshi, M.: "Role of the C-Terminal Region of smg p21, a ras p21-Like Small GTP-Binding Protein, in Membrane and smg p21 GDP/GTP Exchange Protein Interactions." Biol. Chem.266. 2962-2969 (1991)

Hiroyoshi, M.：“smg p21（一种 ras p21 样小 GTP 结合蛋白）的 C 端区域在膜和 smg p21 GDP/GTP 交换蛋白相互作用中的作用。”

Araki, S.: "Role of the C-Terminal Region of smg p25A in Its Interaction with Membranes And the GDP/GTP Exchange Protein." Mol. Cell. Biol.(1991)

Araki, S.：“smg p25A 的 C 末端区域在与膜和 GDP/GTP 交换蛋白相互作用中的作用。”