Primary structure of c-kit: relationship with the CSF-1/PDGF receptor kinase family--oncogenic activation of v-kit involves deletion of extracellular domain and C terminus

EMBO J. 1988 Apr;7(4):1003-11.

Abstract

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)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cats
  • Chromosome Deletion*
  • Chromosome Mapping
  • DNA / genetics
  • Gene Expression Regulation*
  • Genes*
  • Humans
  • Hybrid Cells / cytology
  • Mice
  • Molecular Sequence Data
  • Protein-Tyrosine Kinases / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogenes*
  • RNA / genetics
  • RNA / isolation & purification
  • Receptor, ErbB-2
  • Receptors, Cell Surface / genetics*
  • Receptors, Colony-Stimulating Factor
  • Receptors, Platelet-Derived Growth Factor
  • Retroviridae / genetics*

Substances

  • Proto-Oncogene Proteins
  • Receptors, Cell Surface
  • Receptors, Colony-Stimulating Factor
  • RNA
  • DNA
  • Protein-Tyrosine Kinases
  • Receptor, ErbB-2
  • Receptors, Platelet-Derived Growth Factor

Associated data

  • GENBANK/Y00864