YEAST PHEROMONE SIGNAL TRANSDUCTION

酵母信息素信号转导

• 批准号: 8188011
• 负责人: PETER M PRYCIAK
• 金额: $ 37.22万
• 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/8188011
• 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. PUBLIC HEALTH RELEVANCE: This proposal seeks to shed light on the fundamental mechanisms by which cells respond to external signals. We use a yeast signaling pathway as a model system, but the molecules involved are common to signaling throughout eukaryotic biology, from yeast to humans. The discoveries learned about the basic functions of signaling proteins and pathways under study here will further our understanding of similar signaling events relevant to human health, such as those in vision, hormone responses, and neoplastic growth.

描述（由申请人提供）：细胞功能和行为取决于在细胞外环境中响应信号的能力。在真核细胞中，对外部信号的反应通常在质膜上引发，然后通过信号转导途径在整个细胞中传播，这些途径控制了包括基因表达在内的细胞质和核事件。由于这种信息之间的信息在不同的隔室之间传递，因此信号蛋白的亚细胞定位是其功能的重要方面。此外，还必须将有关响应给定信号响应是否适当的细胞决策与有关细胞生理状态的其他信息集成在一起。该建议使用酿酒酵母的交配反应作为一种模型系统，用于使用分子遗传学和细胞生物学方法来理解真核信号转导。酵母中对交配信息素的响应涉及质膜 - 局部信号传导复合物的动态组装，其中包括在从酵母到人类的各种信号系统中发现的蛋白质，例如PAK-Family激酶，例如杂物蛋白，一种杂种G蛋白，一种MAP KINase酶囊酶，是MAP KINase cascade cascade cascade cascade蛋白。该项目的长期目标是对如何启动和传播通过该途径信号传导的分子了解，重点是支架蛋白的功能，亚细胞定位的作用以及信号传导与细胞周期之间的界面。一个目标是确定MAP激酶级联反对蛋白中的不同域如何调节不同途径激酶之间信号的传递，以及不同域如何相互作用和互动以控制定位和功能。另一个项目将探测信号蛋白如何限制在质膜处的离散区域，以及这如何影响信号传输的效率和动力学。同样，正在研究的是该信号传导途径中蛋白质中的蛋白质在进入细胞周期期间的特定形式的特定形式的机制。总体而言，这些研究将有助于我们对信号转导的一般理解，这与正常细胞和患病细胞都做出分化或增殖的决定的机制有关。 公共卫生相关性：该提案旨在阐明细胞对外部信号反应的基本机制。我们使用酵母信号通路作为模型系统，但是所涉及的分子在整个真核生物生物学（从酵母到人类）中的信号常见。这些发现了解了此处研究的信号蛋白和途径的基本功能，将进一步了解与人类健康相关的类似信号事件，例如视力，激素反应和肿瘤生长。