ENZYME BIOSYNTHESIS IN DEVELOPMENT--ROLE OF CYCLIC AMP

该项目的主要目的是阐明cAMP的作用 “系统”在细胞黏菌Dictyostelius中的发育 盘状骨。CAMP依赖的蛋白激酶及其催化和 将重点研究调节性亚单位的潜在作用 作为不同发展阶段和不同阶段之间过渡的触发器 用于细胞分化为孢子和柄细胞的分叉。 全酶及其亚基的特性将参照 合成的时间进程，它们的性质和细胞和 发育过程中的亚细胞定位。比较研究(在 与另一个实验室合作)结构域和相关氨基 黏菌和哺乳动物cAMP依赖蛋白的酸序列 可以设想使用激活剂。 将检查盘状芽孢杆菌的发育突变株是否存在可能的缺陷 在cAMP依赖的蛋白激酶和新的突变体将被选择用于 酶的异常。 CAMP依赖的蛋白激酶的底物将用 关于细胞和亚细胞的位置，磷酸化时间和 出现在突变体中。 将尝试克隆编码调控基因的基因 DictyostelialcAMP依赖的蛋白激酶的亚基。 该项目与健康相关的意义在于 CAMP作为多种激素作用的细胞介质 网柄苔藓作为发育研究模型的相关性及其意义 异常现象。

The major aim of the project is the elucidation of the role of the cAMP "system" in the development of the cellular slime mold, Dictyostelium discoideum. The cAMP-dependent protein kinase and its catalytic and regulatory subunits will be studied with emphasis on their potential role as triggers for the transitions between different stages of development and for the bifurcation of cellular differentiation into spores and stalk cells. The holoenzyme and its subunits will be characterized with respect to the time course of synthesis, changes in their properties and cellular and subcellular location during development. Comparative studies (in collaboration with another laboratory) of the domains and relevant amino acid sequences of the slime mold and mammalian cAMP-dependent protein kinases are envisaged. Develomental mutants of D. discoideum will be examined for possible defects in the cAMP-dependent protein kinase and new mutants will be selected for abnormalities of the enzyme. Substrates of the cAMP-dependent protein kinase will be characterized with respect to cellular and subcellular location, time of phosphorylation and occurrence in mutants. An attempt will be made to clone the gene which codes for the regulatory subunit of the Dictyostelium cAMP-dependent protein kinase. The health-related significance of the project lies in the central role of cAMP as the cellular mediator of the effects of many hormones and in the relevance of Dictyostelium as a model for the study of development and its abnormalities.