Yeast Pheromone Signal Transduction

项目总结/摘要PI/PD：Pryciak，Peter M. 正常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， 信号通常起始于质膜，然后通过信号传递散布到整个细胞中。 转导途径，其控制细胞质和细胞核事件，包括基因表达。而 许多信号通路和它们的分子组成已经被确定，一些研究充分的系统 提供了独特的机会来了解个体的分子和生化特性， 通路成分塑造了系统的整体反应，并以整合积极和消极的方式， 以及负面的监管影响。这项提案通过利用酵母的交配反应来探讨这些问题 酿酒酵母作为理解真核生物信号基本方面的模型系统 转导，通过分子遗传学和细胞生物学方法。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， 从酵母到人类普遍存在，如异源三聚体G蛋白，MAP激酶级联，和 支架蛋白这个项目的长期目标是从分子水平上了解信号传导是如何 通过这一途径启动和传播，强调亚细胞定位的作用， 正调控和负调控的平衡，以及转录反应的控制。一个目标是 研究信号蛋白在质膜上的离散区室的组织， 这如何影响信号传输的效率和动态。另一个项目将探索 控制MAP激酶蛋白激活负反馈环的能力的机制， 通路支架蛋白。同样在研究中的是基因表达程序是如何被激活的。 信息素受两种不同途径MAP激酶的拮抗作用控制。总的来说，这些研究 将有助于我们对信号转导的一般理解，与相关的机制， 正常细胞和病变细胞都作出关于分化或增殖的决定。

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.