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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM030027-21
Application #
6519056
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Program Officer
Anderson, Richard A
Project Start
1982-02-01
Project End
2005-05-31
Budget Start
2002-06-01
Budget End
2003-05-31
Support Year
21
Fiscal Year
2002
Total Cost
$336,122
Indirect Cost
Name
University of Oregon
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
948117312
City
Eugene
State
OR
Country
United States
Zip Code
97403
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Kemp, Hilary A; Sprague Jr, George F (2003) Far3 and five interacting proteins prevent premature recovery from pheromone arrest in the budding yeast Saccharomyces cerevisiae. Mol Cell Biol 23:1750-63
Goehring, April S; Mitchell, David A; Tong, Amy Hin Yan et al. (2003) Synthetic lethal analysis implicates Ste20p, a p21-activated potein kinase, in polarisome activation. Mol Biol Cell 14:1501-16
Rivers, D M; Sprague Jr, G F (2003) Autocrine activation of the pheromone response pathway in matalpha2- cells is attenuated by SST2- and ASG7-dependent mechanisms. Mol Genet Genomics 270:225-33
Goehring, April S; Rivers, David M; Sprague Jr, George F (2003) Urmylation: a ubiquitin-like pathway that functions during invasive growth and budding in yeast. Mol Biol Cell 14:4329-41
Keniry, Megan E; Sprague Jr, George F (2003) Identification of p21-activated kinase specificity determinants in budding yeast: a single amino acid substitution imparts Ste20 specificity to Cla4. Mol Cell Biol 23:1569-80

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