Yeast Pheromone Signal Transduction

项目摘要/摘要PI/PD：Pryciak，Peter M. 正确的细胞功能和行为取决于对细胞外环境中信号做出反应的能力 并就是否扩散做出适当的决定。在真核细胞中，对外部环境的反应 信号通常在质膜上启动，然后通过信号在细胞内传播 转导途径，控制细胞质和核事件，包括基因表达。而当 已经确定了许多信号通路及其分子组成，一些研究得很好的系统 提供独特的机会来了解个体的分子和生化特性 通路组件塑造了系统的整体反应，并以一种整合了这两种积极反应的方式 以及负面的监管效应。这项建议通过利用酵母的交配反应来探索这些问题。 酿酒酵母作为理解真核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的方法。酵母菌交配信息素的反应 涉及到质膜定位的信号复合体的动态组装，其中包括蛋白质 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如何 通过这一途径被启动和传播，重点是亚细胞定位的作用， 正负调控的平衡，以及转录反应的控制。一个目标将是 研究信号蛋白在质膜上组织成离散的隔间，以及 这对信号传输的效率和动态有何影响。另一个项目将调查 控制MAP激酶蛋白通过抑制激活负反馈环的能力的机制 该途径以蛋白质为支架。还在调查的还有基因表达程序是如何被 信息素受两种不同途径的MAPK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 无论是正常细胞还是疾病细胞，都会决定是分化还是增殖。

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.