Yeast Pheromone Signal Transduction

项目摘要/摘要 PI/PD：Pryciak, Peter M. 适当的细胞功能和行为取决于对细胞外环境中信号的反应能力 并就是否扩散做出适当的决定。在真核细胞中，对外界的反应 信号通常在质膜处启动，然后通过信号传播到整个细胞 转导途径，控制细胞质和核事件，包括基因表达。同时 许多信号传导途径及其分子成分已被识别，一些经过充分研究的系统 提供独特的机会来了解个体的分子和生化特性 路径组件塑造系统的整体响应，并以整合积极的方式 和负面监管影响。该提案通过利用酵母的交配反应来探讨这些问题 酿酒酵母作为了解真核信号基本方面的模型系统 通过分子遗传学和细胞生物学方法进行转导。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 从酵母到人类中普遍存在，例如异源三聚体 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角度了解信号传导的机制 通过该途径启动和传播，重点是亚细胞定位的作用， 正负调节的平衡以及转录反应的控制。目标之一是 研究信号蛋白在质膜上组织成离散的区室，以及 这如何影响信号传输的效率和动态。另一个项目将探讨 控制 MAP 激酶蛋白通过抑制激活负反馈环的能力的机制 途径支架蛋白。还在研究的是基因表达程序如何被激活 信息素由两种不同途径 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，以及信号转导机制的相关性 正常细胞和患病细胞都会做出有关分化或增殖的决定。

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.