title: Regulation of yeast G protein signaling by the kinases that activate the AMPK homolog Snf1.
abstract: Extracellular signals, such as nutrients and hormones, cue intracellular pathways to produce adaptive responses. Often, cells must coordinate their responses to multiple signals to produce an appropriate outcome. We showed that components of a glucose-sensing pathway acted on components of a heterotrimeric guanine nucleotide-binding protein (G protein)-mediated pheromone signaling pathway in the yeast Saccharomyces cerevisiae. We demonstrated that the G protein α subunit Gpa1 was phosphorylated in response to conditions of reduced glucose availability and that this phosphorylation event contributed to reduced pheromone-dependent stimulation of mitogen-activated protein kinases, gene transcription, cell morphogenesis, and mating efficiency. We found that Elm1, Sak1, and Tos3, the kinases that phosphorylate Snf1, the yeast homolog of adenosine monophosphate-activated protein kinase (AMPK), in response to limited glucose availability, also phosphorylated Gpa1 and contributed to the diminished mating response. Reg1, the regulatory subunit of the phosphatase PP1 that acts on Snf1, was likewise required to reverse the phosphorylation of Gpa1 and to maintain the mating response. Thus, the same kinases and phosphatase that regulate Snf1 also regulate Gpa1. More broadly, these results indicate that the pheromone signaling and glucose-sensing pathways communicate directly to coordinate cell behavior.
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Sarah T
authors.initials: ST
authors.lastname: Clement
authors.forename: Gauri
authors.initials: G
authors.lastname: Dixit
authors.forename: Henrik G
authors.initials: HG
authors.lastname: Dohlman
mesh_terms: D004789:Enzyme Activation / Q000502:physiology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics / Q000378:metabolism*; D010675:Pheromones / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D010675:Pheromones; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C411302:ELM1 protein, S cerevisiae; C071570:SNF1-related protein kinases; C094326:PRK1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C502450:TOS3 protein, S cerevisiae; D054645:Protein Phosphatase 1; C070829:REG1 protein, S cerevisiae; C084293:GPA1 protein, S cerevisiae; D043802:GTP-Binding Protein alpha Subunits, Gq-G11