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.
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