Kit signal transduction

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 transmembrane type III tyrosine kinase receptor (molecular weight 145-160 kd) which displays extensive homology with other members of this tyrosine kinase receptor family, such as platelet-derived growth factor (PDGF) and colony-stimulating 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 and 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 that 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 of these isoforms, however, remains unclear. These two isoforms have been reported to coexist in normal tissues at a ratio of 1:5 (kit A:kit). This ratio varies considerably in patients with acute myelogenous leukemia. Kit is expressed on mast cells, hematopoietic stem cells, melanocytes, gametocytes, intraepithelial lymphocytes, and interstitial cells of cajal.