ENZYME BIOSYNTHESIS IN DEVELOPMENT--ROLE OF CYCLIC AMP

酶生物合成在发育中的作用——环磷酸腺苷的作用

• 批准号: 3232867
• 负责人: BEN H LEICHTLING
• 金额: $ 12.65万
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-05-01 至 1989-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3232867
• 关键词: Dictyostelium; affinity labeling; cell differentiation; cyclic AMP; cytogenetics; enzyme mechanism; fungal genetics; gel electrophoresis; genetic transcription; histogenesis; immunochemistry; membrane proteins; molecular cloning; phosphoproteins; phosphorylation; protein biosynthesis; protein kinase A; protein sequence; scintillation counter; spores; temperature sensitive mutant

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.

该项目的主要目的是阐明 cAMP 的作用 细胞粘菌盘基网柄菌发育中的“系统” 盘状体。 cAMP依赖性蛋白激酶及其催化和 将研究监管亚单位，重点关注其潜在作用 作为不同发展阶段之间过渡的触发因素 用于细胞分化为孢子和茎细胞的二叉。 全酶及其亚基将根据以下方面进行表征 合成的时间过程、其性质和细胞的变化 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）的域和相关氨基 粘菌和哺乳动物 cAMP 依赖性蛋白的酸序列 设想了激酶。 将检查 D. discoideum 的发育突变体是否存在可能的缺陷 在 cAMP 依赖性蛋白激酶中，新的突变体将被选择 酶的异常。 cAMP 依赖性蛋白激酶的底物特征为 关于细胞和亚细胞位置、磷酸化时间和 发生在突变体中。 将尝试克隆编码调控的基因 盘基网柄菌 cAMP 依赖性蛋白激酶的亚基。 该项目与健康相关的意义在于其核心作用 cAMP 作为许多激素作用的细胞介质，在 盘基网柄菌作为发育及其研究模型的相关性 异常。