title: Functional organization of the S. cerevisiae phosphorylation network.
abstract: Reversible protein phosphorylation is a signaling mechanism involved in all cellular processes. To create a systems view of the signaling apparatus in budding yeast, we generated an epistatic miniarray profile (E-MAP) comprised of 100,000 pairwise, quantitative genetic interactions, including virtually all protein and small-molecule kinases and phosphatases as well as key cellular regulators. Quantitative genetic interaction mapping reveals factors working in compensatory pathways (negative genetic interactions) or those operating in linear pathways (positive genetic interactions). We found an enrichment of positive genetic interactions between kinases, phosphatases, and their substrates. In addition, we assembled a higher-order map from sets of three genes that display strong interactions with one another: triplets enriched for functional connectivity. The resulting network view provides insights into signaling pathway regulation and reveals a link between the cell-cycle kinase, Cak1, the Fus3 MAP kinase, and a pathway that regulates chromatin integrity during transcription by RNA polymerase II.
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, 94158, USA.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Fiedler
authors.forename: Hannes
authors.initials: H
authors.lastname: Braberg
authors.forename: Monika
authors.initials: M
authors.lastname: Mehta
authors.forename: Gal
authors.initials: G
authors.lastname: Chechik
authors.forename: Gerard
authors.initials: G
authors.lastname: Cagney
authors.forename: Paromita
authors.initials: P
authors.lastname: Mukherjee
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Silva
authors.forename: Michael
authors.initials: M
authors.lastname: Shales
authors.forename: Sean R
authors.initials: SR
authors.lastname: Collins
authors.forename: Sake
authors.initials: S
authors.lastname: van Wageningen
authors.forename: Patrick
authors.initials: P
authors.lastname: Kemmeren
authors.forename: Frank C P
authors.initials: FC
authors.lastname: Holstege
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Weissman
authors.forename: Michael-Christopher
authors.initials: MC
authors.lastname: Keogh
authors.forename: Daphne
authors.initials: D
authors.lastname: Koller
authors.forename: Kevan M
authors.initials: KM
authors.lastname: Shokat
authors.forename: Nevan J
authors.initials: NJ
authors.lastname: Krogan
mesh_terms: D000107:Acetylation; D006657:Histones / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases