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The roles of heterotrimeric GTP-binding proteins in signal transduction

异源三聚体 GTP 结合蛋白在信号转导中的作用

基本信息

批准号：
05271102
负责人：
KATADA Toshiaki
金额：
$ 124.93万
依托单位：
The University of Tokyo (Faculty of Pharmaceutical Sciences)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05271102/
关键词：
GTP-binding proteins Second messengers Membrane receptors Ion channels Effectors Phosphorylation Signal transduction

项目摘要

This research project was organized by ten and a couple of investigators in order to study the roles of alphabetagamma-heterotrimeric GTP-binding proteins (G proteins) in signal transduction from 1993 to 1995. The major findings obtained in this research project are summarized as follows. 1) The cDNAs of membrane-bound receptors that coupled to G proteins were cloned. Such included a novel photo-receptor, pinopsin, which may play an important role in the circadian rhythm of melatonin synthesis, and various types of prostaglandin receptors. 2) The betagamma subunits of G proteins stimulated the phosphorylation of G protein-coupled membrane receptors (GR) such as muscarinic acetylcholine receptors by GR kinases (GRKs). This receptor phosphorylation by GRKs appeared to be involved in the internalization of the phosphorylated receptor molecules. 3) Wortmannin was found to be a specific inhibitor of phosphoinositide (PI) 3-kinase. Using this specific inhibitor, PI 3-kinase was shown to be involved signal transduction pathways mediated through two different types of membrane receptors, one possessing tyrosine kinase activity and the other activating G proteins. 4) Phospholipase D activity was stimulated not only by G proteins but also by small GTP-binding proteins such as Rho and ARF.5) The Post-translational modification of G proteins, fatty-acid addition to alpha subunits, isoprenylation and phosphorylation of gamma subunits, playd important roles in the functional regulation of the signal-transducing proteins.

该研究项目由十名和几名研究人员组织，旨在研究 1993 年至 1995 年间字母γ-异三聚体 GTP 结合蛋白（G 蛋白）在信号转导中的作用。该研究项目获得的主要发现总结如下。 1) 克隆了与G蛋白偶联的膜结合受体的cDNA。其中包括一种新型光感受器松视蛋白（pinopsin），它可能在褪黑激素合成的昼夜节律中发挥重要作用，以及各种类型的前列腺素受体。 2）G蛋白的βγ亚基通过GR激酶（GRK）刺激G蛋白偶联膜受体（GR）的磷酸化，例如毒蕈碱乙酰胆碱受体。 GRK 的这种受体磷酸化似乎与磷酸化受体分子的内化有关。 3) Wortmannin被发现是磷酸肌醇(PI) 3-激酶的特异性抑制剂。使用这种特定的抑制剂，PI 3-激酶被证明参与通过两种不同类型的膜受体介导的信号转导途径，一种具有酪氨酸激酶活性，另一种具有激活G蛋白。 4) 磷脂酶 D 活性不仅受到 G 蛋白的刺激，还受到小的 GTP 结合蛋白（如 Rho 和 ARF）的刺激。 5) G 蛋白的翻译后修饰、α 亚基的脂肪酸添加、γ 亚基的异戊二烯化和磷酸化，在信号转导蛋白的功能调节中发挥着重要作用。