Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases

Mol Cell. 2020 Aug 6;79(3):504-520.e9. doi: 10.1016/j.molcel.2020.07.001. Epub 2020 Jul 23.

Abstract

Protein kinases are essential for signal transduction and control of most cellular processes, including metabolism, membrane transport, motility, and cell cycle. Despite the critical role of kinases in cells and their strong association with diseases, good coverage of their interactions is available for only a fraction of the 535 human kinases. Here, we present a comprehensive mass-spectrometry-based analysis of a human kinase interaction network covering more than 300 kinases. The interaction dataset is a high-quality resource with more than 5,000 previously unreported interactions. We extensively characterized the obtained network and were able to identify previously described, as well as predict new, kinase functional associations, including those of the less well-studied kinases PIM3 and protein O-mannose kinase (POMK). Importantly, the presented interaction map is a valuable resource for assisting biomedical studies. We uncover dozens of kinase-disease associations spanning from genetic disorders to complex diseases, including cancer.

Keywords: cancer; disease module; interaction network; kinome; protein complexes; protein kinases; proteomics; signaling regulation; systems biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computational Biology / methods
  • Datasets as Topic
  • Gene Expression Regulation
  • Gene Ontology
  • Gene Regulatory Networks*
  • Genetic Diseases, Inborn / enzymology
  • Genetic Diseases, Inborn / genetics*
  • Genetic Diseases, Inborn / pathology
  • Humans
  • Metabolic Networks and Pathways / genetics
  • Molecular Sequence Annotation
  • Muscular Dystrophies / enzymology
  • Muscular Dystrophies / genetics
  • Muscular Dystrophies / pathology
  • Neoplasms / enzymology
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Neurodegenerative Diseases / enzymology
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / pathology
  • Protein Interaction Mapping / methods
  • Protein Kinases / chemistry
  • Protein Kinases / classification
  • Protein Kinases / genetics*
  • Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Signal Transduction

Substances

  • Proto-Oncogene Proteins
  • POMK protein, human
  • Protein Kinases
  • PIM3 protein, human
  • Protein-Serine-Threonine Kinases