Global mapping of protein phosphorylation events identifies Ste20, Sch9 and the cell-cycle regulatory kinases Cdc28/Pho85 as mediators of fatty acid starvation responses in Saccharomyces cerevisiae.
Synthesis, degradation, and metabolism of fatty acids are strictly coordinated to meet the nutritional and energetic needs of cells and organisms. In the absence of exogenous fatty acids, proliferation and growth of the yeast Saccharomyces cerevisiae depends on endogenous synthesis of fatty acids, which is catalysed by fatty acid synthase. In the present study, we have used quantitative proteomics to examine the cellular response to inhibition of fatty acid synthesis in Saccharomyces cerevisiae. We have identified approximately 2000 phosphorylation sites of which more than 400 have been identified as being regulated in a temporal manner in response to inhibition of fatty acid synthesis by cerulenin. By bioinformatic analysis of these phosphorylation events, we have identified the cell cycle kinases Cdc28 and Pho85, the PAK kinase Ste20 as well as the protein kinase Sch9 as central mediators of the cellular response to inhibition of fatty acid synthesis.
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark.
Dennis
D
Pultz
Martin V
MV
Bennetzen
Steven Vestergaard
SV
Rødkær
Christine
C
Zimmermann
Jorrit M
JM
Enserink
Jens S
JS
Andersen
Nils J
NJ
Færgeman
D017489:CDC28 Protein Kinase, S cerevisiae / Q000737:chemistry / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*
D005227:Fatty Acids; D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C071569:SCH9 protein kinase; D017346:Protein Serine-Threonine Kinases; C530964:SCH9 protein, S cerevisiae; D017489:CDC28 Protein Kinase, S cerevisiae; D018844:Cyclin-Dependent Kinases; C058605:PHO85 protein, S cerevisiae; D020930:MAP Kinase Kinase Kinases; C078754:STE20 protein, S cerevisiae