PT  - JOURNAL ARTICLE
AU  - Schulz, Juliane Caroline
AU  - Zampieri, Mattia
AU  - Wanka, Stefanie
AU  - von Mering, Christian
AU  - Sauer, Uwe
TI  - Large-scale functional analysis of the roles of phosphorylation in yeast metabolic pathways
AID  - 10.1126/scisignal.2005602
DP  - 2014 Nov 25
TA  - Science Signaling
PG  - rs6--rs6
VI  - 7
IP  - 353
4099  - http://stke.sciencemag.org/content/7/353/rs6.short
4100  - http://stke.sciencemag.org/content/7/353/rs6.full
SO  - Sci. Signal.2014 Nov 25; 7
AB  - 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.