HORMONAL REGULATION OF CELLULAR METABOLISM

本项目主要研究蛋白激酶和蛋白质的功能。 激素启动的细胞外信号转导中的磷酸酶， 神经递质、生长因子和抗原。共价改性 蛋白质的磷酸化/去磷酸化起着核心作用 在介导由配体-受体引起的许多细胞事件中 各种第二信使的互动和生成。几个 蛋白激酶，特别是钙/磷脂/二酰甘油- 刺激蛋白激酶C家族，并已被磷酸酶 大鼠脑提取液用于蛋白质底物的鉴定 被这些酶修饰的。已分离出几种新的蛋白质 离子交换层析和反相层析及其部分 氨基酸序列测定。磷脂和磷脂的作用 钙结合蛋白、钙调蛋白和S-100蛋白 这些蛋白质的磷酸化/去磷酸化正在进行 调查过了。此外，蛋白激酶C的修饰 底物，神经颗粒素，通过过氧化氢等氧化剂 而一氧化氮已经被证明影响了激酶催化的 磷酸化。这些新蛋白的cDNA的分子克隆 激酶C底物正在研发中。白纹伊蚊的基因组结构 中枢神经系统特异性蛋白激酶同工酶及其底物神经颗粒素， 已被阐明。控制组织特异性的机制 而这两个基因的发育阶段调控表达是 目前正在接受调查。

This project focuses on the functions of protein kinases and protein phosphatases in transducing extracellular signals initiated by hormones, neurotransmitters, growth factors, and antigens. Covalent modification of proteins by phosphorylation/dephosphorylation plays a central role in mediating many cellular events resulting from ligand-receptor interaction and generation of a variety of second messengers. Several protein kinases, especially the Ca2+/phospholipid/diacylglycerol- stimulated protein kinase C family, and phosphatases have been prepared from rat brain for the identification of protein substrates modified by these enzymes. Several novel proteins have been isolated by ion-exchange and reverse phase chromatography and their partial amino acid sequences determined. The effects of phospholipids and Ca2+-binding proteins, calmodulin, and S-100 protein on the phosphorylation/dephosphorylation of these proteins are being investigated. In addition, modification of the protein kinase C substrate, neurogranin, by oxidizing agents such as hydrogen peroxide and nitric oxide has been shown to influence the kinase-catalyzed phosphorylation. Molecular cloning of the cDNAs of these novel protein kinase C substrates is in progress. The genomic structures of the CNS-specific protein kinase ~ isozyme and its substrate, neurogranin, have been elucidated. The mechanisms controlling the tissue-specific and developmental stage-regulated expression of these two genes are currently being investigated.