title: The protein interaction landscape of the human CMGC kinase group.
abstract: Cellular 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.
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Markku
authors.initials: M
authors.lastname: Varjosalo
authors.forename: Salla
authors.initials: S
authors.lastname: Keskitalo
authors.forename: Audrey
authors.initials: A
authors.lastname: Van Drogen
authors.forename: Helka
authors.initials: H
authors.lastname: Nurkkala
authors.forename: Anton
authors.initials: A
authors.lastname: Vichalkovski
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
authors.forename: Matthias
authors.initials: M
authors.lastname: Gstaiger
mesh_terms: D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D038341:Glycogen Synthase Kinases / Q000378:metabolism*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D060066:Protein Interaction Maps; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D020543:Proteome; D013379:Substrate Specificity; D053719:Tandem Mass Spectrometry; D014158:Transcription, Genetic
chemical_list: D020543:Proteome; C066780:Clk dual-specificity kinases; D011505:Protein-Tyrosine Kinases; D038341:Glycogen Synthase Kinases; D017346:Protein Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases; D020928:Mitogen-Activated Protein Kinases