title: PKA and Sch9 control a molecular switch important for the proper adaptation to nutrient availability.
abstract: In the yeast Saccharomyces cerevisiae, PKA and Sch9 exert similar physiological roles in response to nutrient availability. However, their functional redundancy complicates to distinguish properly the target genes for both kinases. In this article, we analysed different phenotypic read-outs. The data unequivocally showed that both kinases act through separate signalling cascades. In addition, genome-wide expression analysis under conditions and with strains in which either PKA and/or Sch9 signalling was specifically affected, demonstrated that both kinases synergistically or oppositely regulate given gene targets. Unlike PKA, which negatively regulates stress-responsive element (STRE)- and post-diauxic shift (PDS)-driven gene expression, Sch9 appears to exert additional positive control on the Rim15-effector Gis1 to regulate PDS-driven gene expression. The data presented are consistent with a cyclic AMP (cAMP)-gating phenomenon recognized in higher eukaryotes consisting of a main gatekeeper, the protein kinase PKA, switching on or off the activities and signals transmitted through primary pathways such as, in case of yeast, the Sch9-controlled signalling route. This mechanism allows fine-tuning various nutritional responses in yeast cells, allowing them to adapt metabolism and growth appropriately.
authors.affiliation: Functional Biology, Katholieke Universiteit Leuven, Kasteelpark Arenberg, B-3001 Leuven-Heverlee, Belgium.
authors.forename: Johnny
authors.initials: J
authors.lastname: Roosen
authors.forename: Kristof
authors.initials: K
authors.lastname: Engelen
authors.forename: Kathleen
authors.initials: K
authors.lastname: Marchal
authors.forename: Janick
authors.initials: J
authors.lastname: Mathys
authors.forename: Gerard
authors.initials: G
authors.lastname: Griffioen
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cameroni
authors.forename: Johan M
authors.initials: JM
authors.lastname: Thevelein
authors.forename: Claudio
authors.initials: C
authors.lastname: De Virgilio
authors.forename: Bart
authors.initials: B
authors.lastname: De Moor
authors.forename: Joris
authors.initials: J
authors.lastname: Winderickx
mesh_terms: D000222:Adaptation, Physiological; D003470:Culture Media; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D005947:Glucose / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014198:Trehalase / Q000378:metabolism
chemical_list: D003470:Culture Media; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C071569:SCH9 protein kinase; D017868:Cyclic AMP-Dependent Protein Kinases; D014198:Trehalase; D005947:Glucose