YEAST PHEROMONE SIGNAL TRANSDUCTION

酵母信息素信号转导

• 批准号: 8322014
• 负责人: PETER M PRYCIAK
• 金额: $ 36.27万
• 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 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8322014
• 关键词: Automobile Driving; Behavior; Binding Sites; Biological; Biological Models; Biology; Cell Cycle; Cell Cycle Regulation; Cell membrane; Cell physiology; Cells; Communication; Complex; Cyclin-Dependent Kinases; Cyclins; Decision Making; Defect; Docking; Ensure; Environment; Eukaryota; Eukaryotic Cell; Event; Family; Feedback; G-substrate; Gene Expression; Goals; Health; Heterotrimeric GTP-Binding Proteins; Hormones; Human; In Vitro; Individual; Investigation; Knowledge; Learning; Light; MAP Kinase Gene; MAP Kinase Modules; Mediating; Membrane; Modeling; Molecular; Molecular Genetics; Molecular Probes; Mutation; Neoplasms; Nuclear; PH Domain; Partner in relationship; Pathway interactions; Pheromone; Phosphorylation; Phosphorylation Site; Phosphotransferases; Physiological; Play; Process; Property; Proteins; Reaction; Recruitment Activity; Regulation; Role; Saccharomyces cerevisiae; Scaffolding Protein; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Signaling Protein; Site; Specificity; Stimulus; System; Time; Vision; Yeasts; base; cell behavior; dimer; extracellular; in vitro Assay; in vivo; mutant; novel; protein complex; receptor; response; scaffold; tool; transmission process

DESCRIPTION (provided by applicant): Cell function and behavior depends on the ability to respond to signals in the extracellular environment. In eukaryotic cells, response to external signals is commonly initiated at the plasma membrane and subsequently disseminated throughout the cell by signal transduction pathways, which control cytoplasmic and nuclear events including gene expression. Because of this transfer of information between different compartments, the subcellular localization of signaling proteins is an important aspect of their function. In addition, cellular decisions about whether it is appropriate to respond to a given signal must also be integrated with other information about the physiological status of the cell. This proposal uses the mating reaction of the yeast Saccharomyces cerevisiae as a model system for understanding eukaryotic signal transduction, using a molecular genetics and cell biological approach. Response to mating pheromones in yeast involves the dynamic assembly of plasma membrane-localized signaling complexes, which include proteins found ubiquitously in a variety of signaling systems from yeast to humans, such as a PAK-family kinase, a heterotrimeric G protein, a MAP kinase cascade, and a scaffold protein. The long-term objective of this project is to gain a molecular understanding of how signaling through this pathway is initiated and propagated, with an emphasis on the function of scaffold proteins, the role of subcellular localization, and the interface between signaling and the cell cycle. One goal will be to determine how distinct domains in the MAP kinase cascade scaffold protein, Ste5, regulate the transmission of signal between different pathway kinases, and how different domains interact and coordinate with each other in order to control localization and function. Another project will probe how signaling proteins become restricted to discrete regions at the plasma membrane, and how this impacts the efficiency and dynamics of signal transmission. Also under investigation will be the mechanism by which proteins in this signaling pathway are recognized by specific forms of the cyclin-Cdk kinase during entry into the cell cycle. Overall, these studies will contribute to our general understanding of signal transduction, with relevance to the mechanisms by which both normal and diseased cells make decisions regarding differentiation or proliferation.

描述（由申请人提供）：细胞功能和行为取决于对细胞外环境中信号的响应能力。在真核细胞中，对外部信号的反应通常在质膜处起始，随后通过信号转导途径散布在整个细胞中，所述信号转导途径控制细胞质和核事件，包括基因表达。由于这种不同区室之间的信息传递，信号蛋白的亚细胞定位是其功能的一个重要方面。此外，细胞决定是否适合对给定信号作出反应，还必须与有关细胞生理状态的其他信息相结合。该建议使用酵母酿酒酵母的交配反应作为理解真核细胞信号转导的模型系统，使用分子遗传学和细胞生物学方法。酵母中对交配信息素的反应涉及质膜定位信号复合物的动态组装，所述质膜定位信号复合物包括在从酵母到人类的各种信号系统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。该项目的长期目标是从分子水平上了解通过该途径的信号传导是如何启动和传播的，重点是支架蛋白的功能，亚细胞定位的作用以及信号传导和细胞周期之间的界面。一个目标是确定MAP激酶级联支架蛋白Ste 5中的不同结构域如何调节不同途径激酶之间的信号传递，以及不同结构域如何相互作用和相互协调以控制定位和功能。另一个项目将探索信号蛋白如何被限制在质膜的离散区域，以及这如何影响信号传输的效率和动态。还将研究该信号通路中的蛋白质在进入细胞周期期间被特定形式的细胞周期蛋白-Cdk激酶识别的机制。总的来说，这些研究将有助于我们对信号转导的一般理解，与正常和病变细胞决定分化或增殖的机制有关。