title: Kit as a human oncogenic tyrosine kinase.
abstract: 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.
authors.affiliation: Shionogi Pharmaceutical Company, 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan. yukihiko.kitamura@shionogi.co.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Kitamura
authors.forename: S
authors.initials: S
authors.lastname: Hirotab
mesh_terms: D000818:Animals; D001549:Benzamides; D019281:Dimerization; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D000068877:Imatinib Mesylate; D007946:Leukemia, Mast-Cell / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D009373:Neoplasms, Germ Cell and Embryonal / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000502:physiology*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction; D013329:Structure-Activity Relationship
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit