The protein interaction landscape of the human CMGC kinase group

Cell Rep. 2013 Apr 25;3(4):1306-20. doi: 10.1016/j.celrep.2013.03.027. Epub 2013 Apr 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Chromatography, High Pressure Liquid
  • Cyclin-Dependent Kinases / metabolism*
  • Glycogen Synthase Kinases / metabolism*
  • Humans
  • Mitogen-Activated Protein Kinases / metabolism*
  • Protein Interaction Maps*
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein-Tyrosine Kinases / metabolism*
  • Proteome
  • Substrate Specificity
  • Tandem Mass Spectrometry
  • Transcription, Genetic


  • Proteome
  • Clk dual-specificity kinases
  • Protein-Tyrosine Kinases
  • Glycogen Synthase Kinases
  • Protein Serine-Threonine Kinases
  • Cyclin-Dependent Kinases
  • Mitogen-Activated Protein Kinases