title: Two glucose-sensing pathways converge on Rgt1 to regulate expression of glucose transporter genes in Saccharomyces cerevisiae.
abstract: The yeast Saccharomyces cerevisiae deploys two different types of glucose sensors on its cell surface that operate in distinct glucose signaling pathways: the glucose transporter-like Snf3 and Rgt2 proteins and the Gpr1 receptor that is coupled to Gpa2, a G-protein alpha subunit. The ultimate target of the Snf3/Rgt2 pathway is Rgt1, a transcription factor that regulates expression of HXT genes encoding glucose transporters. We have found that the cAMP-dependent protein kinase A (PKA), which is activated by the Gpr1/Gpa2 glucose-sensing pathway and by a glucose-sensing pathway that works through Ras1 and Ras2, catalyzes phosphorylation of Rgt1 and regulates its function. Rgt1 is phosphorylated in vitro by all three isoforms of PKA, and this requires several serine residues located in PKA consensus sequences within Rgt1. PKA and the consensus serine residues of Rgt1 are required for glucose-induced removal of Rgt1 from the HXT promoters and for induction of HXT expression. Conversely, overexpression of the TPK genes led to constitutive expression of the HXT genes. The PKA consensus phosphorylation sites of Rgt1 are required for an intramolecular interaction that is thought to regulate its DNA binding activity. Thus, two different glucose signal transduction pathways converge on Rgt1 to regulate expression of glucose transporters.
authors.affiliation: Mississippi Functional Genomics Network (MFGN), Department of Biological Sciences, University of Southern Mississippi, Hattiesburg, Mississippi 39406, USA. jeongho.kim@mfgn.usm.edu
authors.forename: Jeong-Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Mark
authors.initials: M
authors.lastname: Johnston
mesh_terms: D000595:Amino Acid Sequence; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative; D007527:Isoenzymes / Q000378:metabolism; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011401:Promoter Regions, Genetic; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; C109334:GPR1 protein, S cerevisiae; D044385:GTP-Binding Protein alpha Subunits; D051246:Glucose Transport Proteins, Facilitative; C090594:HXT1 protein, S cerevisiae; D007527:Isoenzymes; D009004:Monosaccharide Transport Proteins; C102114:RGT1 protein, S cerevisiae; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D017868:Cyclic AMP-Dependent Protein Kinases; C083907:Gpa2 protein, S cerevisiae; D005947:Glucose