PROTEIN KINASE NETWORKS AND SPORULATION IN S. CEREVISIAE

酿酒酵母中的蛋白激酶网络和孢子形成

• 批准号: 6900259
• 负责人: EDWARD P WINTER
• 金额: $ 29.52万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6900259
• 关键词: Saccharomyces cerevisiae; biological signal transduction; cell cycle; cyclin dependent kinase; developmental genetics; enzyme activity; enzyme mechanism; fungal genetics; gene expression; immunoprecipitation; meiosis; microorganism culture; mitogen activated protein kinase; molecular cloning; molecular genetics; mutant; phosphorylation; serine threonine protein kinase; spindle pole body; sporogenesis

DESCRIPTION (provided by applicant): The reversible phosphorylation of proteins is a major regulatory mechanism that controls cell cycle progression and development in all eukaryotic organisms. Meiosis and spore formation in yeast (sporulation) provides an outstanding model system to study protein kinase signaling pathways. Similar to developmental programs in higher eukaryotes, induction of sporulation is controlled by a combination of cell-type and environmental signals. Once initiated, a transcriptional cascade of cell-type specific genes ultimately leads to a cell that is genetically and biochemically distinct from the starting cell. A protein kinase network has been identified that controls multiple steps in meiotic development. A central component of this network is the activating kinase Cak1. During sporulation Cak1 is required for activation of the MAP kinase homolog Smk1, the CDK-like kinase Ime2, and the CDK Cdc28. The CAK1, IME2 and SMK1 genes are tightly regulated by the transcriptional cascade of sporulation. This network controls meiotic progression at multiple self-reinforcing steps through DNA-binding and chromatin-modifying regulatory proteins. The goal of this proposal is to identify new components of the Cak1/Ime2/Smk1 protein kinase network, to elucidate molecular mechanisms that control its activities, and to identify targets that couple signaling to meiotic progression. The specific aims of the proposal are: 1- Elucidate how Cak1 activates the Smk1 MAP kinase. 2- Elucidate how Ime2 is regulated by phosphorylation 3- Elucidate molecular mechanisms that regulate mid-late sporulation-specific gene expression, and 4- Identify negative regulators of the Smk1 pathway using genetic suppression approaches. These studies will provide mechanistic insights into how protein kinase networks control developmental programs in general and meiotic development in particular.

描述（由申请人提供）：蛋白质的可逆磷酸化是控制所有真核生物细胞周期进程和发育的主要调节机制。酵母的减数分裂和孢子形成（孢子形成）为研究蛋白激酶信号通路提供了一个出色的模型系统。类似于高等真核生物的发育程序，孢子形成的诱导受细胞类型和环境信号的组合控制。一旦启动，细胞类型特异性基因的转录级联最终导致与起始细胞在遗传和生物化学上不同的细胞。已经鉴定出控制减数分裂发育中多个步骤的蛋白激酶网络。这个网络的一个中心组成部分是激活激酶Cak 1。在孢子形成过程中，需要Cak 1激活MAP激酶同源物Smk 1、CDK样激酶Ime 2和CDK Cdc 28。CAK 1、IME 2和SMK 1基因受到孢子形成的转录级联的严格调控。该网络通过DNA结合和染色质修饰调节蛋白在多个自我增强步骤控制减数分裂进程。该提案的目标是确定Cak 1/Ime 2/Smk 1蛋白激酶网络的新组件，阐明控制其活动的分子机制，并确定将信号传导耦合到减数分裂进程的靶点。本研究的具体目的是：1-阐明Cak 1如何激活Smk 1 MAP激酶。2-阐明Ime 2如何受磷酸化调节3-阐明调节中晚期孢子形成特异性基因表达的分子机制，和4-使用遗传抑制方法鉴定Smk 1途径的负调节因子。这些研究将为蛋白激酶网络如何控制一般的发育程序，特别是减数分裂发育提供机理上的见解。