Catalytic mechanisms and regulation of protein kinases

Methods Enzymol. 2014;548:1-21. doi: 10.1016/B978-0-12-397918-6.00001-X.


Protein kinases transfer a phosphoryl group from ATP onto target proteins and play a critical role in signal transduction and other cellular processes. Here, we review the kinase kinetic and chemical mechanisms and their application in understanding kinase structure and function. Aberrant kinase activity has been implicated in many human diseases, in particular cancer. We highlight applications of technologies and concepts derived from kinase mechanistic studies that have helped illuminate how kinases are regulated and contribute to pathophysiology.

Keywords: B-Raf; Bisubstrate analog; Chemical rescue; EGFR; Erlotinib; Inhibitor; Lapatinib; Src; Transition state.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / chemistry
  • Adenosine Triphosphate / metabolism
  • Animals
  • Biocatalysis / drug effects*
  • Humans
  • Models, Molecular*
  • Mutation
  • Phosphorylation / drug effects
  • Protein Conformation
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinases / chemistry
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Protein Processing, Post-Translational / drug effects
  • Substrate Specificity


  • Protein Kinase Inhibitors
  • Adenosine Triphosphate
  • Protein Kinases