Yeast Pheromone Signal Transduction

酵母信息素信号转导

• 批准号: 10252901
• 负责人: PETER M PRYCIAK
• 金额: $ 39.94万
• 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 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10252901
• 关键词: Attenuated; Behavior; Biochemical; Biological; Biological Models; Biology; Cell Nucleus; Cell division; Cell membrane; Cell physiology; Cells; Complex; Decision Making; Disease; Docking; Dose; Environment; Enzymes; Equilibrium; Eukaryotic Cell; Event; Feedback; Fluorescence Microscopy; Gene Expression; Genes; Genetic Transcription; Goals; Health; Heterotrimeric GTP-Binding Proteins; Hormones; Human; Individual; Investigation; Ligands; Light; Logic; MAP Kinase Modules; Measures; Mediating; Membrane; Mitogen-Activated Protein Kinases; Modeling; Molecular; Molecular Genetics; Morphogenesis; Neoplasms; Nuclear Accidents; Output; Partner in relationship; Pathway interactions; Pheromone; Phosphorylation; Phosphorylation Site; Phosphotransferases; Proliferating; Property; Protein Kinase; Proteins; Reaction; Regulation; Repression; Role; Saccharomyces cerevisiae; Saccharomycetales; Scaffolding Protein; Shapes; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Signaling Protein; Site; Stimulus; System; Time; Transcriptional Regulation; Vision; Yeasts; cell behavior; extracellular; insight; prevent; programs; promoter; receptor; recruit; response; scaffold; theories; tool; transcriptome; transmission process

Project Summary/Abstract PI/PD: Pryciak, Peter M. Proper cell function and behavior depends on the ability to respond to signals in the extracellular environment and make appropriate decisions about whether or not to proliferate. In eukaryotic cells, responses to external signals are commonly initiated at the plasma membrane and then disseminated throughout the cell by signal transduction pathways, which control both cytoplasmic and nuclear events including gene expression. While many signaling pathways and their molecular components have been identified, some well-studied systems offer unique opportunities to understand how the molecular and biochemical properties of the individual pathway components shape the overall response of the system, and in a manner that integrates both positive and negative regulatory effects. This proposal explores such issues by using the mating reaction of the yeast Saccharomyces cerevisiae as a model system to understand fundamental aspects of eukaryotic signal transduction, via a molecular genetic and cell biological approach. The response to yeast mating pheromones involves a dynamic assembly of plasma membrane-localized signaling complexes, which include proteins found ubiquitously from yeast to humans such as 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 role of subcellular localization, the balance of positive and negative regulation, and the control of transcriptional responses. One goal will be to investigate the organization of signaling proteins into discrete compartments at the plasma membrane, and how this impacts the efficiency and dynamics of signal transmission. Another project will probe the mechanisms that control the ability of a MAP kinase protein to activate a negative feedback loop by inhibiting the pathway scaffold protein. Also under investigation will be how the gene expression program activated by pheromone is controlled by antagonistic effects of of two different pathway MAP kinases. 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.

项目摘要/摘要PI/PD：Pryciak，Peter M. 正确的细胞功能和行为取决于在细胞外环境中响应信号的能力 并就是否扩散做出适当的决定。在真核细胞中，对外部的反应 信号通常在质膜上启动，然后通过信号在整个单元格中传播 控制胞质和核事件（包括基因表达）的转导途径。尽管 已经确定了许多信号通路及其分子成分 提供独特的机会来了解个人的分子和生化特性如何 途径成分塑造了系统的整体响应，并以整合两个正的方式 和负调节效应。该提案通过使用酵母的交配反应来探讨此类问题 酿酒酵母作为一种模型系统，以了解真核信号的基本方面 转导，通过分子遗传和细胞生物学方法。对酵母交配信息素的反应 涉及质膜 - 定位信号复合物的动态组装，其中包括蛋白质 从酵母到人类的普遍发现，例如异三聚体G蛋白，MAP激酶级联和A 脚手架蛋白。该项目的长期目标是对信号传导的分子了解 通过该途径启动和传播，重点是亚细胞定位的作用，即 正面和负调节的平衡以及转录响应的控制。一个目标是 调查信号蛋白在质膜上的离散隔室中的组织，并 这如何影响信号传输的效率和动态。另一个项目将调查 控制MAP激酶蛋白能力激活负反馈回路的能力的机制 途径支架蛋白。同样正在研究的基因表达程序如何通过 信息素受两个不同途径MAP激酶的拮抗作用控制。总体而言，这些研究 将有助于我们对信号转导的一般理解，并与之相关 正常细胞和患病细胞都就分化或增殖做出决定。