Functional organization of the S. cerevisiae phosphorylation network.
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.
Fiedler
Dorothea
D
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, 94158, USA.
Braberg
Hannes
H
Mehta
Monika
M
Chechik
Gal
G
Cagney
Gerard
G
Mukherjee
Paromita
P
Silva
Andrea C
AC
Shales
Michael
M
Collins
Sean R
SR
van Wageningen
Sake
S
Kemmeren
Patrick
P
Holstege
Frank C P
FC
Weissman
Jonathan S
JS
Keogh
Michael-Christopher
MC
Koller
Daphne
D
Shokat
Kevan M
KM
Krogan
Nevan J
NJ
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
D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases