title: The role of the Snf1 kinase in the adaptive response of Saccharomyces cerevisiae to alkaline pH stress.
abstract: Alkaline pH stress invokes a potent and fast transcriptional response in Saccharomyces cerevisiae that includes many genes repressed by glucose. Certain mutants in the glucose-sensing and -response pathways, such as those lacking the Snf1 kinase, are sensitive to alkalinization. In the present study we show that the addition of glucose to the medium improves the growth of wild-type cells at high pH, fully abolishes the snf1 alkali-sensitive phenotype and attenuates high pH-induced Snf1 phosphorylation at Thr(210). Lack of Elm1, one of the three upstream Snf1 kinases (Tos3, Elm1 and Sak1), markedly increases alkali sensitivity, whereas the phenotype of the triple mutant tos3 elm1 sak1 is even more pronounced than that of snf1 cells and is poorly rescued by glucose supplementation. DNA microarray analysis reveals that about 75% of the genes induced in the short term by high pH are also induced by glucose scarcity. Snf1 mediates, in full or in part, the activation of a significant subset (38%) of short-term alkali-induced genes, including those encoding high-affinity hexose transporters and phosphorylating enzymes. The induction of genes encoding enzymes involved in glycogen, but not trehalose, metabolism is largely dependent of the presence of Snf1. Therefore the function of Snf1 in adaptation to glucose scarcity appears crucial for alkaline pH tolerance. Incorporation of micromolar amounts of iron and copper to a glucose-supplemented medium resulted in an additive effect and allows near-normal growth at high pH, thus indicating that these three nutrients are key limiting factors for growth in an alkaline environment.
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Universitat Autónoma de Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Casamayor
authors.forename: Raquel
authors.initials: R
authors.lastname: Serrano
authors.forename: María
authors.initials: M
authors.lastname: Platara
authors.forename: Carlos
authors.initials: C
authors.lastname: Casado
authors.forename: Amparo
authors.initials: A
authors.lastname: Ruiz
authors.forename: Joaquín
authors.initials: J
authors.lastname: Ariño
mesh_terms: D000222:Adaptation, Physiological; D003300:Copper / Q000494:pharmacology; D003470:Culture Media; D004268:DNA-Binding Proteins / Q000378:metabolism; D005800:Genes, Fungal; D005947:Glucose / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000494:pharmacology; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D013312:Stress, Physiological; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D003470:Culture Media; D004268:DNA-Binding Proteins; D009004:Monosaccharide Transport Proteins; C102114:RGT1 protein, S cerevisiae; C112512:RGT2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D003300:Copper; D007501:Iron; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; D005947:Glucose