Protein tyrosine kinases: autoregulation and small-molecule inhibition

Curr Opin Struct Biol. 2002 Dec;12(6):735-41. doi: 10.1016/s0959-440x(02)00383-4.


Receptor and non-receptor protein tyrosine kinases (PTKs) are essential enzymes in cellular signaling processes that regulate cell growth, differentiation, migration and metabolism. The kinase activity of PTKs is tightly controlled through steric, autoregulatory mechanisms, as well as by the action of protein tyrosine phosphatases. Recent structural studies have revealed several modes of autoregulation governing the catalytic state of these enzymes. Aberrant catalytic activity of many PTKs, via mutation or overexpression, plays an important role in numerous pathological conditions, including cancer. Structural studies of the Abl tyrosine kinase domain in complex with the small-molecule inhibitor STI571 provide a molecular basis for understanding the specificity determinants of this highly successful drug used in the treatment of chronic myeloid leukemia.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Benzamides
  • Binding Sites
  • Enzyme Inhibitors / metabolism
  • Imatinib Mesylate
  • Models, Molecular
  • Piperazines / metabolism
  • Protein Structure, Tertiary*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / chemistry*
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins c-abl / chemistry
  • Proto-Oncogene Proteins c-abl / metabolism
  • Pyrimidines / metabolism
  • src-Family Kinases / chemistry
  • src-Family Kinases / metabolism


  • Benzamides
  • Enzyme Inhibitors
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-abl
  • src-Family Kinases