title: Large-scale functional analysis of the roles of phosphorylation in yeast metabolic pathways.
abstract: Protein phosphorylation is a widespread posttranslational modification that regulates almost all cellular functions. To investigate the large number of phosphorylation events with unknown functions, we monitored the concentrations of several hundred intracellular metabolites in Saccharomyces cerevisiae yeast strains with deletions of 118 kinases or phosphatases. Whereas most deletion strains had no detectable difference in growth compared to wild-type yeast, two-thirds of deletion strains had alterations in metabolic profiles. For about half of the kinases and phosphatases encoded by the deleted genes, we inferred specific regulatory roles on the basis of knowledge about the affected metabolic pathways. We demonstrated that the phosphatase Ppq1 was required for metal homeostasis. Combining metabolomic data with published phosphoproteomic data in a stoichiometric model enabled us to predict functions for phosphorylation in the regulation of 47 enzymes. Overall, we provided insights and testable predictions covering greater than twice the number of known phosphorylated enzymes in yeast, suggesting extensive phosphorylation-dependent regulation of yeast metabolism.
authors.affiliation: Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule (ETH) Zürich, 8093 Zürich, Switzerland.
authors.forename: Juliane Caroline
authors.initials: JC
authors.lastname: Schulz
authors.affiliation: Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule (ETH) Zürich, 8093 Zürich, Switzerland.
authors.forename: Mattia
authors.initials: M
authors.lastname: Zampieri
authors.affiliation: Institute of Molecular Life Sciences and Swiss Institute of Bioinformatics, University of Zürich, 8057 Zürich, Switzerland.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Wanka
authors.affiliation: Institute of Molecular Life Sciences and Swiss Institute of Bioinformatics, University of Zürich, 8057 Zürich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: von Mering
authors.affiliation: Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule (ETH) Zürich, 8093 Zürich, Switzerland. sauer@imsb.biol.ethz.ch.
authors.forename: Uwe
authors.initials: U
authors.lastname: Sauer
mesh_terms: D004734:Energy Metabolism / Q000235:genetics; D000431:Ethanol / Q000378:metabolism; D017353:Gene Deletion; D005947:Glucose / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008345:Manganese / Q000494:pharmacology; D053858:Metabolic Networks and Pathways / Q000235:genetics; D055442:Metabolome; D010269:Paraquat / Q000494:pharmacology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism*; D017510:Protein Folding; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D010750:Phosphoproteins; D029701:Saccharomyces cerevisiae Proteins; D000431:Ethanol; D008345:Manganese; D010770:Phosphotransferases; D010744:Phosphoric Monoester Hydrolases; D005947:Glucose; D008239:Lysine; D010269:Paraquat