RGULATION OF CYCLIC GMP PHOSPHODIESTERASE BY GZ

广州市对环GMP磷酸二酯酶的规定

基本信息

批准号：
6178844
负责人：
ANDREW B. NIXON
金额：
$ 3.92万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-08-01 至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/6178844
关键词：
G protein biological signal transduction cell line enzyme activity enzyme complex gene expression hydrolysis immunoprecipitation phosphodiesterases protein binding protein purification tissue /cell culture transfection yeast two hybrid system

项目摘要

Much progress has been made in our understanding of how cells transmit external signals via specific cell surface receptors to internal targets. Receptor binding initiates intracellular signaling pathways, often through the activation of heterotrimeric G-proteins, eventually leading to a specific cellular response. Gz is one such heterotrimeric G-protein that exhibits unique biochemical features and limited tissue distribution. Although initial characterization of Gz has provided insight into the biochemical characterization of the protein, the downstream target(s) of Gz remain undefined. Preliminary studies utilizing the yeast two-hybrid system suggest that Gzalpha may possibly interact with the gamma subunit of cyclic GMP phosphodiesterase. G- protein regulation of phosphodiesterases has not been described outside sensory tissues, but recent identification of both Gz and phosphodiesterase gamma in various regions of the brain supports the view that this may occur. We postulate that phosphodiesterase gamma is a natural effector for Gz. Both in vitro studies and studies in intact cells will be conducted to determine whether phosphodiesterase gamma and Gzalpha associate and whether this interaction can modulate cyclic nucleotide levels by activating the phosphodiesterase complex. The proposed studies will quite possibly result in the first characterization the interaction of Gzalpha with a specific effector molecule, namely phosphodiesterase gamma.

我们对细胞如何传递信息的理解已经取得了很大进展外部信号通过特定的细胞表面受体传递至内部目标。受体结合启动细胞内信号传导途径，通常通过异源三聚体 G 蛋白的激活，最终导致特定的细胞反应。 Gz 就是这样一种异源三聚体 G蛋白表现出独特的生化特征和有限的组织分配。尽管 Gz 的初步特征表明深入了解蛋白质的生化特征 Gz 的下游目标仍未确定。初步研究利用酵母双杂交系统表明 Gzalpha 可能与环 GMP 磷酸二酯酶的 γ 亚基相互作用。 G- 外界尚未描述磷酸二酯酶的蛋白质调节感觉组织，但最近鉴定出 Gz 和大脑各个区域的磷酸二酯酶γ支持认为这种情况可能会发生。我们假设磷酸二酯酶 γ 是 Gz 的天然效应器。体外研究和完整研究将进行细胞以确定磷酸二酯酶γ和 Gzalpha 关联以及这种相互作用是否可以调节循环通过激活磷酸二酯酶复合物来提高核苷酸水平。这拟议的研究很可能会产生第一个结果表征 Gzalpha 与特定效应器的相互作用分子，即磷酸二酯酶γ。