The proto-oncogene c-kit was first identified as the cellular homologue of
the oncogene v-kit, isolated from the retrovirus HZ-4-feline sarcoma, which
causes multicentric fibrosarcomas.(2) This proto-oncogene encodes a transm
embrane type III tyrosine kinase receptor (molecular weight 145-160 kd) whi
ch displays extensive homology with other members of this tyrosine kinase r
eceptor family, such as platelet-derived growth factor (PDGF) and colony-st
imulating factor-1 (CSF-1 or c-fms).(104) In humans, the c-kit gene maps to
chromosome 4 (4q11 12), which is in close proximity to the PDGF receptor a
nd to the epidermal growth factor (EGF) receptor. Kit protein has also been
shown to be identical to the product of the murine dominant white-spotting
W locus on chromosome 5 and as such is integral to the development of mast
cells and hematopoiesis.(18)
Alternative splicing results in two naturally occurring isoforms of kit tha
t contain (kit A) or lack (kit) four amino acids (Gly Asn Asn Lys) at codon
510 just outside the transmembrane domain.(85) The biologic significance o
f these isoforms, however, remains unclear. These two isoforms have been re
ported to coexist in normal tissues at a ratio of 1:5 (kit A:kit). This rat
io varies considerably in patients with acute myelogenous leukemia.
Kit is expressed on mast cells, hematopoietic stem cells, melanocytes, game
tocytes, intraepithelial lymphocytes, and interstitial cells of cajal.