GENETIC REGULATION OF YEAST CELL TYPE

细胞内信号转导通路为真核细胞响应外界刺激并产生相应的生理反应提供了途径。这些通路可能相当复杂，包含分支点，因此生理反应也可能同样复杂。即使在最好的研究案例中，通路活动是如何被调节的，以及它是如何实现全方位的生理反应的，我们也不清楚。此外，近年来的观察表明，在同一细胞中运作的信号转导途径通常具有共同的成分，这加剧了我们理解上的差距。这种认识提出了一个问题，即当细胞对特定的环境线索作出反应时，如何维持通路的完整性。所有这些问题的例证都发生在酵母的信号转导途径中。这里提出的实验有两个主要目标。首先是了解不同的环境线索如何激活惊人相似的信号转导途径，但却导致不同的生理输出。在这个广泛的目标中，我们将确定允许质膜蛋白Sho1激活不同信号通路以响应不同环境线索的机制。我们还将分离其他两种信号转导途径（信息素反应途径和侵袭性生长途径）特异性激活的突变体。这个广泛目标的第二个方面是确定蛋白激酶Ste20连接核心信号转导途径和细胞形态发生事件的机制。第二个大目标是关注信息素反应途径。我们将确定Far3在G1期促进细胞周期阻滞的机制，我们将确定控制信号衰减和对信息素信号的适应的成分。

Intracellular signal transduction pathways provide a meats for eukaryotic cells to respond to external stimuli and mount an appropriate physiological response. The pathways can be quite sophisticated, containing branch points, and hence the physiological response can be likewise sophisticated. Even in the best studies cases, how pathway activity is regulated and how it achieves a full spectrum of physiological responses is not understood. Moreover, the gaps in our understanding are compounded by the observations made in recent years that signal transduction pathways that operate in the same cells often share components. This realization raises the question as to how pathway integrity is maintained when a cell is responding to a particular environmental cue. Illustrations of all these issues occur in signal transduction pathways found in the yeast Saccharomyces cerevisiae. There are two broad goals for the experiments proposed here. The first is to understand how distinct environmental cues can activate strikingly similar signal transduction pathways but nonetheless lead to distinct physiological outputs. In this broad goal, we will determine the mechanisms that allow the plasma membrane protein, Sho1, to activate distinct signaling pathways in response to different environmental cues. We will also isolate mutants in which the specificity of activation in two other signal transduction pathways, the pheromone response pathway and the invasive growth pathway, is abrogated. A second aspect of this broad goal is to determine the mechanism by which the protein kinase Ste20 connects core signal transduction pathways to cellular morphogenetic events. The second broad goal is to focus on the pheromone response pathway. We will determine the mechanism by which Far3 contributes to cell cycle arrest in the G1 phase, and we will identify components that control signal attenuation and adaptation to the pheromone signal.