The protein kinase domains of v‐kit, the oncogene of the acute transforming feline retrovirus HZ4‐FeSV (HZ4‐feline sarcoma virus), CSF‐1R (macrophage colony stimulating factor receptor) and PDGFR (platelet derived growth factor receptor) display extensive homology. Because of the close structural relationship of v‐kit, CSF‐1R and PDGFR we predicted that c‐kit would encode a protein kinase transmembrane receptor (Besmer et al., 1986a; Yarden et al., 1986). We have now determined the primary structure of murine c‐kit from a DNA clone isolated from a brain cDNA library. The nucleotide sequence of the c‐kit cDNA predicts a 975 amino acid protein product with a calculated mol. wt of 109.001 kd. It contains an N‐terminal signal peptide, a transmembrane domain (residues 519‐543) and in the C‐terminal half the v‐kit homologous sequences (residues 558‐925). c‐kit therefore contains the features which are characteristic of a transmembrane receptor kinase. Comparison of c‐kit, CSF‐1R and PDGFR revealed a unique structural relationship of these receptor kinases suggesting a common evolutionary origin. The outer cellular domain of c‐kit was shown to be related to the immunoglobulin superfamily. The sites of expression of c‐kit in normal tissue predict a function in the brain and in hematopoietic cells. N‐terminal sequences which include the extracellular domain and the transmembrane domain as well as 50 amino acids from the C‐terminus of c‐kit are deleted in v‐kit. These structural alterations are likely determinants of the oncogenic activation of v‐kit.(ABSTRACT TRUNCATED AT 250 WORDS)

A new acute transforming feline retrovirus, the Hardy-Zuckerman 4 feline sarcoma virus (HZ4-FeSV), has been isolated from a feline fibrosarcoma. The viral genome of HZ4-FeSV contains a new oncogene designated v-kit, has the structure 5' delta gag-kit-delta pol-delta env 3' and specifies a gag-kit polyprotein of relative molecular mass 80,000. The predicted kit amino-acid sequence displays partial homology with tyrosine-specific protein kinase oncogenes. HZ4-FeSV appears to have been generated by transduction of feline c-kit sequences with feline leukaemia virus.