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

基本信息

批准号：
7990577
负责人：
EDWARD P WINTER
金额：
$ 9.4万
依托单位：
THOMAS JEFFERSON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-12-17 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7990577
关键词：
Biological Models Cell Cycle Progression Cells Chromatin Chromatin Remodeling Factor Chromosomal Breaks Collaborations Complex Cyclic AMP-Dependent Protein Kinases DNA Binding Data Development Eukaryota Funding Gene Expression Genes Genetic Genetic Recombination Genetic Suppression Goals Homologous Gene Laboratories Late Promoters Link MAP Kinase Gene MSLN gene Meiosis Methods Mitogen Activated Protein Kinase 1 Mitogen-Activated Protein Kinases Modeling Modification Molecular Molecular Genetics Morphogenesis Nuclear Organism Pathway interactions Phase Phosphorylation Phosphotransferases Protein Kinase Proteins Regulator Genes Reproduction spores Research Personnel Role Saccharomyces cerevisiae Signal Pathway Signal Transduction Testing Time Transcription Coactivator Transcription Repressor/Corepressor Work Yeasts cell type genetic regulatory protein insight nuclear division programs promoter research study response segregation

项目摘要

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体细胞周期进程和发育的主要调节机制。酵母中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。与高等真核生物的发育程序类似，孢子形成的诱导是由细胞类型和环境信号的组合控制的。一旦启动，细胞类型特异性基因的转录级联最终会产生在遗传和生物化学上与起始细胞不同的细胞。已鉴定出控制减数分裂发育多个步骤的蛋白激酶网络。该网络的核心组成部分是激活激酶 Cak1。在孢子形成过程中，Cak1 是 MAP 激酶同系物 Smk1、CDK 样激酶 Ime2 和 CDK Cdc28 激活所必需的。 CAK1、IME2 和 SMK1 基因受到孢子形成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以多个自我强化步骤控制减数分裂进程。该提案的目标是确定 Cak1/Ime2/Smk1 蛋白激酶网络的新组件，阐明控制其活性的分子机制，并确定将信号传导与减数分裂进程耦合的靶点。该提案的具体目标是： 1- 阐明 Cak1 如何激活 Smk1 MAP 激酶。 2- 阐明 Ime2 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，以及 4- 使用基因抑制方法识别 Smk1 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发育程序，特别是减数分裂发育提供机制见解。