Genetic Regulation of Yeast Cell Type

描述（由申请人提供）：细胞通过激活将信号传递至靶蛋白的细胞内信号传导途径来响应细胞外信号，从而使细胞能够产生适当的生理反应。在许多情况下，在相同细胞中运作的信号转导途径共享组件，这就提出了如何维持信号传导特异性的问题。这个问题也得到在酵母酿酒酵母。我们将使用遗传和分子方法来了解赋予特异性的信号转导途径在酵母的机制。由于许多在酵母中起信号作用的蛋白质在其他生物体中也有对应物，包括人类，我们希望我们发现的机制也适用于其他物种。信号转导通路的激活通常导致应答细胞的转录程序发生变化，但信号转导通路也影响转录以外的细胞生物学方面。我们的第二个目标是识别和理解将信息素、丝状生长和渗透传感途径与控制肌动蛋白细胞骨架功能和细胞周期进展的机制联系起来的联系。Ste20是一种具有人类同源物的p21活化蛋白激酶，是与肌动蛋白细胞骨架连接的一个点。第二个联系点是一个研究不足的泛素样系统，我们发现它是丝状生长所必需的。基于缺乏该系统的突变体的表型，我们假设它影响细胞周期的调节。我们将使用遗传和质谱方法来确定Ste20和泛素样系统的目标，并研究这些目标在丝状生长，肌动蛋白细胞骨架功能和细胞周期进程中的作用。

DESCRIPTION (provided by applicant): Cells respond to extracellular cues by activating intracellular signaling pathways that transmit that signal to target proteins, thereby enabling the cell to mount an appropriate physiological response. In a number of cases, signal transduction pathways that operate in the same cell share components, raising questions as to how specificity of signaling is maintained. This issue also obtains in the yeast Saccharomyces cerevisiae. We will use genetic and molecular methods to learn about the mechanisms that confer specificity to signal transduction pathways in yeast. Because many proteins that function in signaling in yeast have counterparts in other organisms, including humans, we expect that mechanisms we discover will apply in other species too. Activation of signal transduction pathways often leads to a change in the transcription program for the responding cell, but signaling pathways also influence facets of cell biology other than transcription. Our second goal is to identify and understand the connections that link the pheromone, filamentous growth, and osmosensing pathways to machinery that controls function of the actin cytoskeleton and progression through the cell cycle. Ste20, a p21-activated protein kinase that has human homologs, is one point of connection to the actin cytoskeleton. A second point of connection is a poorly studied ubiquitin-like system that we discovered is required for filamentous growth. Based on the phenotype of mutants lacking this system, we hypothesize that it influences regulation of the cell cycle. We will use genetic and mass spectrometry approaches to identify targets of Ste20 and of the ubiquitin-like system, and investigate the role of those targets in filamentous growth, actin cytoskeleton function, and cell cycle progression.