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Mol Gen Genet

Title:		Switch-domain mutations in the Saccharomyces cerevisiae G protein alpha-subunit Gpa1p identify a receptor subtype-biased mating defect
Author(s):		DeSimone SM; Kurjan J;
Address:		"Department of Microbiology and Molecular Genetics, Markey Center for Molecular Genetics, University of Vermont, Burlington 05405-0068, USA"
Journal Title:		Mol Gen Genet
Year:		1998
Volume:		257
Issue:		6
Page Number:		662 - 671
DOI:		10.1007/s004380050695
ISSN/ISBN:		0026-8925 (Print) 0026-8925 (Linking)
Abstract:		"The response to pheromone in Saccharomyces cerevisiae involves a heterotrimeric G protein composed of Gpa1p (alpha subunit), Ste4p (beta) and Ste18p (gamma). The switch II region of G alpha subunits is involved in several protein-protein interactions and an intrinsic GTPase activity. To investigate the role of this region of Gpa1p, we have analyzed the effect of switch II mutations. The Q323 analog in G alpha subunits and Ras is implicated in GTP hydrolysis. Mutation of the Q323 residue of Gpa1p resulted in constitutive activation of the pheromone response pathway and eliminated the ability to interact with Ste4p, consistent with a defect in GTPase activity. Mutation of residue A59 of Ras and the analogous G alphas residue has had quite different effects. The analogous Gpa1p G321T mutation resulted in phenotypes consistent with a less severe GTPase defect, but also led to an unexpected mating phenotype: mating was decreased in both mating types, but the defect was 1000-fold more severe in alpha cells than in a cells. In addition the G321T mutation resulted in an unusual pheromone response phenotype. We discuss the possibility that these phenotypes may reflect a differential role for the switch II region in activation by the a- and alpha-factor receptors"
Keywords:		"Fungal Proteins/*genetics/immunology *GTP-Binding Protein alpha Subunits GTP-Binding Protein alpha Subunits, Gq-G11 GTP-Binding Proteins/*genetics/immunology Genes, Fungal/*genetics Genes, Switch/*genetics *Heterotrimeric GTP-Binding Proteins Phenotype Po;"
Notes:		"MedlineDeSimone, S M Kurjan, J eng GM40585/GM/NIGMS NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Germany 1998/05/30 Mol Gen Genet. 1998 Apr; 257(6):662-71. doi: 10.1007/s004380050695"