TY - JOUR
T1 - Functional Organization of the S. cerevisiae Phosphorylation Network
AU - Fiedler, Dorothea
AU - Braberg, Hannes
AU - Mehta, Monika
AU - Chechik, Gal
AU - Cagney, Gerard
AU - Mukherjee, Paromita
AU - Silva, Andrea C.
AU - Shales, Michael
AU - Collins, Sean R.
AU - van Wageningen, Sake
AU - Kemmeren, Patrick
AU - Holstege, Frank C.P.
AU - Weissman, Jonathan S.
AU - Keogh, Michael Christopher
AU - Koller, Daphne
AU - Shokat, Kevan M.
AU - Krogan, Nevan J.
N1 - Funding Information:
The authors thank A. Roguev, C. Kaplan, C.J. Ingles, P. Aguilar, T. Walther, J.H. Morris, and members of the Krogan, Shokat, and Keogh labs for advice and comments. We also thank W.A. Lim for discussion on MAP kinase cascades. We are grateful to A. Chan, E. Cheng, Y. Nijati, and Li Jieying for technical assistance. We thank F. Winston and S. Buratowski for providing yeast strains and B. Strahl, S. Hahn, and D. Morgan for sharing unpublished data. The work was supported by an Ernst Schering Postdoctoral Fellowship (D.F.), the Biophysics Graduate Group at UCSF (H.B.), the National Science Foundation (G.C. and D.K.), the New York Speakers Fund for Biomedical Research (M.-C.K.), the Howard Hughes Medical Institute (K.M.S.), the NIH (N.J.K. and K.M.S.), and Sandler Family Funding (N.J.K.).
PY - 2009/3/6
Y1 - 2009/3/6
N2 - 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.
AB - 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.
KW - SIGNALING
UR - http://www.scopus.com/inward/record.url?scp=61349119934&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2008.12.039
DO - 10.1016/j.cell.2008.12.039
M3 - Article
C2 - 19269370
AN - SCOPUS:61349119934
SN - 0092-8674
VL - 136
SP - 952
EP - 963
JO - Cell
JF - Cell
IS - 5
ER -