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Mol Genet Genomics

Title:		Autocrine activation of the pheromone response pathway in matalpha2- cells is attenuated by SST2- and ASG7-dependent mechanisms
Author(s):		Rivers DM; Sprague GF;
Address:		"Institute of Molecular Biology, University of Oregon, Eugene, OR 97303-1229, USA"
Journal Title:		Mol Genet Genomics
Year:		2003
Volume:		20030916
Issue:		3
Page Number:		225 - 233
DOI:		10.1007/s00438-003-0914-3
ISSN/ISBN:		1617-4615 (Print) 1617-4623 (Linking)
Abstract:		"Yeast mat alpha2 mutants express both mating pheromones and both mating pheromone receptors. They show modest signaling in the pheromone response pathway, as revealed by increased levels of FUS1 transcript, yet are resistant to pheromone treatment. Together, these phenotypes suggest that alpha2- cells undergo autocrine activation of the pheromone response pathway, which is subsequently attenuated. We constructed a regulatable version of the alpha2 gene (GALalpha2) and showed that, upon loss of alpha2 activity, cells exhibit an initial robust response to pheromone that is attenuated within 3 h. We reasoned that the viability of alpha2- cells might be due to attenuation, and therefore performed a genome-wide synthetic lethal screen to identify potential adaptation components. We identified two genes, SST2 and ASG7. Loss of either of these attenuation components results in activation of the pheromone pathway in alpha2- cells. Loss of both proteins causes a more severe phenotype. Sst2 functions as a GTPase activating protein (GAP) for the Galpha subunit of the trimeric G protein. Asg7 is an a -cell specific protein that acts in concert with the alpha-cell specific a -factor receptor, Ste3, to inhibit signaling by Gbetagamma. Hence, our results suggest that mat alpha2 mutants mimic the intracellular signaling events that occur in newly fused zygotes"
Keywords:		"Base Sequence DNA Primers GTPase-Activating Proteins/*genetics *Gene Deletion Gene Expression Regulation, Fungal/*genetics Genes, Fungal Genotype Homeodomain Proteins/*genetics Membrane Proteins/*genetics Molecular Sequence Data Mutagenesis Pheromones/*ph;"
Notes:		"MedlineRivers, D M Sprague, G F Jr eng GM-30027/GM/NIGMS NIH HHS/ HD07348/HD/NICHD NIH HHS/ Research Support, U.S. Gov't, P.H.S. Germany 2003/09/19 Mol Genet Genomics. 2003 Nov; 270(3):225-33. doi: 10.1007/s00438-003-0914-3. Epub 2003 Sep 16"