title: Nutrient sensing systems for rapid activation of the protein kinase A pathway in yeast.
abstract: The cAMP-protein kinase A (PKA) pathway in the yeast Saccharomyces cerevisiae controls a variety of properties that depend on the nutrient composition of the medium. High activity of the pathway occurs in the presence of rapidly fermented sugars like glucose or sucrose, but only as long as growth is maintained. Growth arrest of fermenting cells or growth on a respiratory carbon source, like glycerol or ethanol, is associated with low activity of the PKA pathway. We have studied how different nutrients trigger rapid activation of the pathway. Glucose and sucrose activate cAMP synthesis through a G-protein-coupled receptor system, consisting of the GPCR Gpr1, the Galpha protein Gpa2 and its RGS protein Rgs2. Glucose is also sensed intracellularly through its phosphorylation. Specific mutations in Gpr1 abolish glucose but not sucrose signalling. Activation of the PKA pathway by addition of a nitrogen source or phosphate to nitrogen- or phosphate-starved cells, respectively, is not mediated by an increase in cAMP. Activation by amino acids is triggered by the general amino acid permease Gap1, which functions as a transporter/receptor. Short truncation of the C-terminus results in constitutively activating alleles. Activation by ammonium uses the ammonium permeases Mep1 and Mep2 as receptor. Specific point mutations in Mep2 uncouple signalling from transport. Activation by phosphate is triggered a.o. by the Pho84 phosphate permease. Several mutations in Pho84 separating transport and signalling or triggering constitutive activation have been obtained.
authors.affiliation: Katholieke Universiteit Leuven and Department of Molecular Microbiology, Flanders Interuniversity Institute for Biotechnology, Kasteelpark Arenberg 31, B-3001 Leuven-Heverlee, Flanders, Belgium. johan.thevelein@bio.kuleuven.ac.be
authors.forename: J M
authors.initials: JM
authors.lastname: Thevelein
authors.forename: R
authors.initials: R
authors.lastname: Geladé
authors.forename: I
authors.initials: I
authors.lastname: Holsbeeks
authors.forename: O
authors.initials: O
authors.lastname: Lagatie
authors.forename: Y
authors.initials: Y
authors.lastname: Popova
authors.forename: F
authors.initials: F
authors.lastname: Rolland
authors.forename: F
authors.initials: F
authors.lastname: Stolz
authors.forename: S
authors.initials: S
authors.lastname: Van de Velde
authors.forename: P
authors.initials: P
authors.lastname: Van Dijck
authors.forename: P
authors.initials: P
authors.lastname: Vandormael
authors.forename: A
authors.initials: A
authors.lastname: Van Nuland
authors.forename: K
authors.initials: K
authors.lastname: Van Roey
authors.forename: G
authors.initials: G
authors.lastname: Van Zeebroeck
authors.forename: B
authors.initials: B
authors.lastname: Yan
mesh_terms: D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000378:metabolism*; D013395:Sucrose / Q000378:metabolism
chemical_list: D026901:Membrane Transport Proteins; D010710:Phosphates; D013395:Sucrose; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose