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Science 328 (5981): 1043-1046

Copyright © 2010 by the American Association for the Advancement of Science

A Global Protein Kinase and Phosphatase Interaction Network in Yeast

Ashton Breitkreutz,1,* Hyungwon Choi,2,* Jeffrey R. Sharom,1,3,* Lorrie Boucher,1,* Victor Neduva,4,* Brett Larsen,1 Zhen-Yuan Lin,1 Bobby-Joe Breitkreutz,1 Chris Stark,1 Guomin Liu,1 Jessica Ahn,1 Danielle Dewar-Darch,1 Teresa Reguly,1 Xiaojing Tang,1 Ricardo Almeida,4 Zhaohui Steve Qin,5 Tony Pawson,1,3 Anne-Claude Gingras,1,3,{dagger} Alexey I. Nesvizhskii,2,6,{dagger} Mike Tyers1,3,4,{dagger}

Abstract: The interactions of protein kinases and phosphatases with their regulatory subunits and substrates underpin cellular regulation. We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric analysis of protein complexes. The KPI network contained many dense local regions of interactions that suggested new functions. Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism, whereas interactions of the target of rapamycin complex 1 (TORC1) uncovered new effector kinases in nitrogen and carbon metabolism. An extensive backbone of kinase-kinase interactions cross-connects the proteome and may serve to coordinate diverse cellular responses.

1 Centre for Systems Biology, Samuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ontario, M5G 1X5, Canada.
2 Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
3 Department of Molecular Genetics, University of Toronto, 1 Kings College Circle, Toronto, Ontario, M5S 1A8, Canada.
4 Wellcome Trust Centre for Cell Biology and School of Biological Sciences, University of Edinburgh, Mayfield Road, Edinburgh, EH9 3JR Scotland, UK.
5 Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA.
6 Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: gingras{at}lunenfeld.ca (A.C.G.), nesvi{at}med.umich.edu (A.I.N.), tyers{at}lunenfeld.ca, m.tyers{at}ed.ac.uk (M.T.)


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