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 1,844 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, while 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.
Data generated in this study and interaction annotation notes are available at the custom database search where all interactions can be filtered with user-defined SAINT thresholds. Data supporting this study is also available for download. The open source Significance Analysis of Interactome (SAINT) software is available for download at Sourceforge and from the Nesvizhskii Lab homepage.
CIHR to A.C.G. (MOP-84314), T.P. (MOP-57793) and M.T. (MOP 12246), the Ontario Research Fund to T.P. and A.C.G. (REO#-044), the NIH to M.T. (5R01RR024031) and A.I.N. (CA-126239), an NCIC doctoral student award to J.S., Canada Research Chairs in Functional Genomics and Bioinformatics to M.T and in Functional Proteomics to A.C.G. and a Scottish Universities Life Sciences Alliance Research Professorship and a Royal Society Wolfson Research Merit Award to M.T.