Kit as a human oncogenic tyrosine kinase

Cell Mol Life Sci. 2004 Dec;61(23):2924-31. doi: 10.1007/s00018-004-4273-y.


Signals through Kit receptor tyrosine kinase are essential for development of erythrocytes, melanocytes, germ cells, mast cells and interstitial cells of Cajal (ICCs). Mice and rats with a double gene dose of loss-of-function mutations of Kit show depletion of these cells. Although human homozygotes with loss-of-function mutations of Kit have not been reported, gain-of-function mutations of Kit result in development of tumors from mast cells, germ cells and ICCs in humans. The ICC tumors are called gastrointestinal stromal tumors (GISTs), and GISTs are a good target for the Kit inhibitor imatinib mesylate. The interrelationship between the type of Kit gain-of-function mutations and the therapeutic effect of imatinib mesylate has been well characterized in GISTs. Kit is interesting from both a biological and clinical view-point.

Publication types

  • Review

MeSH terms

  • Animals
  • Benzamides
  • Dimerization
  • Gastrointestinal Stromal Tumors / genetics
  • Gastrointestinal Stromal Tumors / metabolism
  • Homozygote
  • Humans
  • Imatinib Mesylate
  • Leukemia, Mast-Cell / metabolism
  • Mice
  • Models, Biological
  • Mutation
  • Neoplasms / enzymology*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms, Germ Cell and Embryonal / metabolism
  • Piperazines / pharmacology
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / physiology*
  • Pyrimidines / pharmacology
  • Rats
  • Signal Transduction
  • Structure-Activity Relationship


  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Proto-Oncogene Proteins c-kit