Genetic Regulation of Yeast Cell Type

描述(申请人提供)：细胞通过激活细胞内信号通路来响应细胞外信号，该信号通路将信号传递给目标蛋白质，从而使细胞能够做出适当的生理反应。在许多情况下，在相同细胞中运行的信号转导通路共享组件，这引发了如何保持信号特异性的问题。这一问题也在酿酒酵母中获得。我们将使用遗传和分子方法来了解赋予酵母信号转导途径特异性的机制。由于酵母中许多在信号传递中起作用的蛋白质在包括人类在内的其他生物中也有对应的蛋白质，我们预计我们发现的机制也将适用于其他物种。信号转导通路的激活通常会导致反应细胞转录程序的改变，但信号转导通路也会影响细胞生物学的各个方面，而不是转录。我们的第二个目标是识别和理解将信息素、丝状生长和渗透途径与控制肌动蛋白细胞骨架功能和细胞周期进展的机械联系起来。Ste20是一种p21激活的蛋白激酶，具有人类同源物，是肌动蛋白细胞骨架的连接点之一。第二个连接点是一个研究很少的泛素样系统，我们发现它是丝状细胞生长所必需的。根据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学方法识别Ste20和泛素样系统的靶标，并研究这些靶标在丝状生长、肌动蛋白细胞骨架功能和细胞周期进展中的作用。

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.