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The Protein Interaction Landscape of the Human CMGC Kinase Group

2013; Cell Press; Volume: 3; Issue: 4 Linguagem: Inglês

10.1016/j.celrep.2013.03.027

2639-1856

Markku Varjosalo, Salla Keskitalo, Audrey van Drogen, Helka Nurkkala, Anton Vichalkovski, Ruedi Aebersold, Matthias Gstaiger,

Computational Drug Discovery Methods

Highlights•A high-confidence interaction proteome for the human CMGC kinase family•Organization of human CMGC kinases in kinase-kinase subnetworks•Network inference revealed CMGC kinase-substrates modules•Discovery of 108 physical interactions between kinases and disease-associated proteinsSummaryCellular information processing via reversible protein phosphorylation requires tight control of the localization, activity, and substrate specificity of protein kinases, which to a large extent is accomplished by complex formation with other proteins. Despite their critical role in cellular regulation and pathogenesis, protein interaction information is available for only a subset of the 518 human protein kinases. Here we present a global proteomic analysis of complexes of the human CMGC kinase group. In addition to subgroup-specific functional enrichment and modularity, the identified 652 high-confidence kinase-protein interactions provide a specific biochemical context for many poorly studied CMGC kinases. Furthermore, the analysis revealed a kinase-kinase subnetwork and candidate substrates for CMGC kinases. Finally, the presented interaction proteome uncovered a large set of interactions with proteins genetically linked to a range of human diseases, including cancer, suggesting additional routes for analyzing the role of CMGC kinases in controlling human disease pathways.Graphical abstract