title: Control of adaptation to mating pheromone by G protein beta subunits of Saccharomyces cerevisiae.
abstract: The STE4 gene of the yeast Saccharomyces cerevisiae encodes the beta subunit of a heterotrimeric G protein that mediates response to mating pheromones and influences recovery from pheromone-induced growth arrest. To explore how G beta subunits regulate response and recovery (adaptation), we isolated and characterized signaling-defective STE4 alleles (STE4sd). STE4sd mutations resulted in amino acid substitutions in the N-terminal region of Ste4p, proximal to the first of seven repeat units conserved in G protein beta subunits. Genetic tests indicated that STE4sd mutations disrupted functions of Ste4p required for inducing pheromone responses. Wild-type cells that overexpressed STE4sd alleles displayed apparently normal initial responses to pheromone as judged by quantitative mating, G1 arrest and transcriptional assays. However, after undergoing initial G1 arrest, wild-type cells overexpressing STE4sd alleles recovered more quickly from division arrest, suggestive of a hyperadaptive phenotype. Because hyperadaptation occurred when STE4sd alleles were overexpressed in cells lacking Sst1p (Bar1p), Sst2p or the C-terminal domain of the alpha-factor receptor, this phenotype did not involve three principal modes of adaptation in yeast. However, hyperadaptation was abolished when STE4sd mutations were combined in cis with a deletion that removes a segment of Ste4p (residues 310-346) previously implicated in adaptation to pheromone. These results indicate that G beta subunits possess two independent activities, one required for triggering pheromone response and another that promotes adaptation. Potential models for G beta subunit-mediated adaptation are discussed.
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: A V
authors.initials: AV
authors.lastname: Grishin
authors.forename: J L
authors.initials: JL
authors.lastname: Weiner
authors.forename: K J
authors.initials: KJ
authors.lastname: Blumer
mesh_terms: D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D001483:Base Sequence; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D044387:GTP-Binding Protein beta Subunits; D019204:GTP-Binding Proteins / Q000502:physiology*; D020962:Heterotrimeric GTP-Binding Proteins; D000072235:Mating Factor; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction
chemical_list: D005656:Fungal Proteins; D044387:GTP-Binding Protein beta Subunits; D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins; C067576:Ste4 protein, S cerevisiae; D000072235:Mating Factor; D019204:GTP-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins