Homing in: Mechanisms of Substrate Targeting by Protein Kinases

Trends Biochem Sci. 2018 May;43(5):380-394. doi: 10.1016/j.tibs.2018.02.009. Epub 2018 Mar 12.


Protein phosphorylation is the most common reversible post-translational modification in eukaryotes. Humans have over 500 protein kinases, of which more than a dozen are established targets for anticancer drugs. All kinases share a structurally similar catalytic domain, yet each one is uniquely positioned within signaling networks controlling essentially all aspects of cell behavior. Kinases are distinguished from one another based on their modes of regulation and their substrate repertoires. Coupling specific inputs to the proper signaling outputs requires that kinases phosphorylate a limited number of sites to the exclusion of hundreds of thousands of off-target phosphorylation sites. Here, we review recent progress in understanding mechanisms of kinase substrate specificity and how they function to shape cellular signaling networks.

Keywords: enzyme specificity; linear sequence motif; protein interactions; protein kinase; protein phosphorylation.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Humans
  • Phosphorylation
  • Protein Kinases / chemistry
  • Protein Kinases / metabolism*
  • Signal Transduction
  • Substrate Specificity


  • Protein Kinases