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.

journal_name

Cell

journal_title

Cell

authors

Fiedler D,Braberg H,Mehta M,Chechik G,Cagney G,Mukherjee P,Silva AC,Shales M,Collins SR,van Wageningen S,Kemmeren P,Holstege FC,Weissman JS,Keogh MC,Koller D,Shokat KM,Krogan NJ

doi

10.1016/j.cell.2008.12.039

subject

Has Abstract

pub_date

2009-03-06 00:00:00

pages

952-63

issue

5

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(09)00002-6

journal_volume

136

pub_type

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