title: Snf1 Phosphorylates Adenylate Cyclase and Negatively Regulates Protein Kinase A-dependent Transcription in Saccharomyces cerevisiae.
abstract: In eukaryotes, nutrient availability and metabolism are coordinated by sensing mechanisms and signaling pathways, which influence a broad set of cellular functions such as transcription and metabolic pathways to match environmental conditions. In yeast, PKA is activated in the presence of high glucose concentrations, favoring fast nutrient utilization, shutting down stress responses, and boosting growth. On the contrary, Snf1/AMPK is activated in the presence of low glucose or alternative carbon sources, thus promoting an energy saving program through transcriptional activation and phosphorylation of metabolic enzymes. The PKA and Snf1/AMPK pathways share common downstream targets. Moreover, PKA has been reported to negatively influence the activation of Snf1/AMPK. We report a new cross-talk mechanism with a Snf1-dependent regulation of the PKA pathway. We show that Snf1 and adenylate cyclase (Cyr1) interact in a nutrient-independent manner. Moreover, we identify Cyr1 as a Snf1 substrate and show that Snf1 activation state influences Cyr1 phosphorylation pattern, cAMP intracellular levels, and PKA-dependent transcription.
authors: From the Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy, SYSBIO, Centre of Systems Biology, 20126 Milan, Italy.
authors: Raffaele
authors: R
authors: Nicastro
authors: From the Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy, SYSBIO, Centre of Systems Biology, 20126 Milan, Italy.
authors: Farida
authors: F
authors: Tripodi
authors: From the Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy, SYSBIO, Centre of Systems Biology, 20126 Milan, Italy.
authors: Marco
authors: M
authors: Gaggini
authors: From the Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy, SYSBIO, Centre of Systems Biology, 20126 Milan, Italy.
authors: Andrea
authors: A
authors: Castoldi
authors: From the Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy, SYSBIO, Centre of Systems Biology, 20126 Milan, Italy.
authors: Veronica
authors: V
authors: Reghellin
authors: Dipartimento di Patologia Animale, Igiene e Sanità Pubblica Veterinaria-Biochemistry, University of Milano, 20133 Milan, Italy, and the Filarete Foundation, 20139 Milan, Italy.
authors: Simona
authors: S
authors: Nonnis
authors: Dipartimento di Patologia Animale, Igiene e Sanità Pubblica Veterinaria-Biochemistry, University of Milano, 20133 Milan, Italy, and the Filarete Foundation, 20139 Milan, Italy.
authors: Gabriella
authors: G
authors: Tedeschi
authors: From the Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy, SYSBIO, Centre of Systems Biology, 20126 Milan, Italy, paola.coccetti@unimib.it.
authors: Paola
authors: P
authors: Coccetti
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D055162:Biocatalysis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009154:Mutation; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D024101:Mitochondrial Proteins; C114727:RRF1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: AMP-activated kinase (AMPK); Cyr1; adenylate cyclase (adenylyl cyclase); cyclic AMP (cAMP); protein kinase A (PKA); yeast