YEAST PHEROMONE SIGNAL TRANSDUCTION

酵母信息素信号转导

• 批准号: 7208153
• 负责人: PETER M PRYCIAK
• 金额: $ 33.57万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7208153
• 关键词: Behavior; Binding; Biological; Biological Models; Cell Cycle; Cell Cycle Progression; Cell Cycle Regulation; Cell Polarity; Cell division; Cell membrane; Cells; Commit; Complex; Environment; Eukaryota; Eukaryotic Cell; Family; Foundations; G1 Arrest; Genetic; Goals; Heterotrimeric GTP-Binding Proteins; Human; Individual; Investigation; Localized; MAP Kinase Gene; MAP Kinase Modules; Mediating; Membrane; Mitotic Cell Cycle; Mitotic spindle; Modeling; Molecular; Partner in relationship; Pathway interactions; Pheromone; Phosphotransferases; Physiological; Prevalence; Proliferating; Proteins; Reagent; Role; Route; Saccharomyces cerevisiae; Scaffolding Protein; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Structure; Surveys; System; Testing; Yeasts; base; extracellular; in vivo; intracellular protein transport; protein localization location; response; scaffold; trafficking

DESCRIPTION (provided by applicant): Cellular behavior is commonly controlled by signals in the extracellular environment. The effects can be dramatic, such as the decision to proliferate or to differentiate, and so the responses must be highly regulated and carefully orchestrated. While many signaling pathways and their molecular components have been identified, some well-studied systems offer a unique opportunity to test how multiple components achieve a unified cellular response that integrates information from different subcellular regions as well as information about the physiological status of the cell. The signal transduction pathway that is activated by extracellular mating pheromones in the yeast Saccharomyces cerevisiae presents an ideal model system in which to probe the intricacies that are built into a cellular response. Signaling in this system involves the dynamic assembly of plasma membrane-localized signaling complexes, which include proteins found ubiquitously in a variety of signaling pathways from yeast to humans, such as a PAK-family kinase, a heterotrimeric G protein, a MAP kinase cascade, and a scaffold protein. Here we make use of a rich foundation of information and genetic reagents to test several intriguing models about the mechanisms that propagate intracellular signaling and their interface with cell biological structures, with particular emphasis on the role of subcellular localization. One goal will be to determine how membrane recruitment of the MAP kinase cascade scaffold protein Ste5 amplifies signaling through the kinase cascade, and whether this signaling occurs predominantly between or within individual scaffold molecules. Another goal will be to dissect the multiple routes by which the mating MAP kinase cascade can inhibit the mitotic cell cycle, and to determine why it is important for this signaling pathway to be inactivated as cells commit to division. Also under investigation will be the role of a small membrane-binding domain in the PAK-family kinase Ste20, and the prevalence of similar domains in other polarized proteins. Overall, we expect these studies to contribute to a sophisticated understanding of signal transduction by revealing mechanisms that are built into signaling systems to allow dynamic and integrative responses within a cell.

描述（由申请人提供）：细胞行为通常由细胞外环境中的信号控制。影响可能是戏剧性的，例如决定增殖或分化，因此反应必须受到高度调控和精心策划。虽然已经确定了许多信号通路及其分子组分，但一些经过充分研究的系统提供了一个独特的机会来测试多个组分如何实现统一的细胞反应，该反应整合了来自不同亚细胞区域的信息以及有关细胞生理状态的信息。在酵母酿酒酵母中由细胞外交配信息素激活的信号转导途径提出了一个理想的模型系统，在该系统中探测细胞反应中的复杂性。该系统中的信号传导涉及质膜定位的信号传导复合物的动态组装，所述信号传导复合物包括在从酵母到人类的各种信号传导途径中普遍存在的蛋白质，如PAK家族激酶、异源三聚体G蛋白、MAP激酶级联和支架蛋白。在这里，我们利用丰富的信息和遗传试剂的基础来测试几个有趣的模型，传播细胞内信号的机制及其与细胞生物学结构的接口，特别强调亚细胞定位的作用。一个目标是确定MAP激酶级联支架蛋白Ste5的膜募集如何通过激酶级联放大信号传导，以及这种信号传导是否主要发生在单个支架分子之间或内部。另一个目标是剖析交配MAP激酶级联可以抑制有丝分裂细胞周期的多种途径，并确定为什么当细胞致力于分裂时，这种信号通路被失活很重要。也正在调查中的PAK家族激酶Ste20中的小膜结合结构域的作用，以及其他极化蛋白中类似结构域的普遍性。总的来说，我们希望这些研究有助于揭示信号转导的机制，内置于信号系统，使动态和整合的反应在一个细胞内的复杂的理解。