RT Journal
A1 Sharifpoor, Sara
A1 van Dyk, Dewald
A1 Costanzo, Michael
A1 Baryshnikova, Anastasia
A1 Friesen, Helena
A1 Douglas, Alison C.
A1 Youn, Ji-Young
A1 VanderSluis, Benjamin
A1 Myers, Chad L.
A1 Papp, Balázs
A1 Boone, Charles
A1 Andrews, Brenda J.
T1 Functional wiring of the yeast kinome revealed by global analysis of genetic network motifs
JF Genome Research 
JO Genome Research 
YR 2012 
FD April 01 
VO 22 
IS 4 
SP 791 
OP 801 
DO 10.1101/gr.129213.111 
UL http://genome.cshlp.org/content/22/4/791.abstract 
AB A combinatorial genetic perturbation strategy was applied to interrogate the yeast kinome on a genome-wide scale. We assessed the global effects of gene overexpression or gene deletion to map an integrated genetic interaction network of synthetic dosage lethal (SDL) and loss-of-function genetic interactions (GIs) for 92 kinases, producing a meta-network of 8700 GIs enriched for pathways known to be regulated by cognate kinases. Kinases most sensitive to dosage perturbations had constitutive cell cycle or cell polarity functions under standard growth conditions. Condition-specific screens confirmed that the spectrum of kinase dosage interactions can be expanded substantially in activating conditions. An integrated network composed of systematic SDL, negative and positive loss-of-function GIs, and literature-curated kinase–substrate interactions revealed kinase-dependent regulatory motifs predictive of novel gene-specific phenotypes. Our study provides a valuable resource to unravel novel functional relationships and pathways regulated by kinases and outlines a general strategy for deciphering mutant phenotypes from large-scale GI networks.