Transforming potential of the c-fms proto-oncogene (CSF-1 receptor).
The c-fms proto-oncogene encodes a transmembrane glycoprotein that is probably identical to the receptor for the macrophage colony stimulating factor, CSF-1. Forty C-terminal amino acids of the normal receptor are replaced by 11 unrelated residues in the feline v-fms oncogene product, deleting a C-terminal tyrosine residue (Tyr969) whose phosphorylation might negatively regulate the receptor kinase activity. We show that the human c-fms gene stimulates growth of mouse NIH 3T3 cells in agar in response to human recombinant CSF-1, indicating that receptor transduction is sufficient to induce a CSF-1 responsive phenotype. Although cells transfected with c-fms genes containing either Tyr969 or Phe969 were not transformed, cotransfection of these genes with CSF-1 complementary DNA induced transformation, with c-fms(Phe969) showing significantly more activity than c-fms(Tyr969). In the absence of CSF-1, chimaeric v-fms/c-fms genes encoding the wild-type c-fms C terminus were poorly transforming, whereas chimaeras bearing Phe969 were as transforming as v-fms. Thus, the Phe969 mutation, although not in itself sufficient to induce transformation, activates the oncogenic potential of c-fms in association with an endogenous ligand or in conjunction with mutations elsewhere in the c-fms gene that confer ligand-independent signals for growth.
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003115:Colony-Stimulating Factors; D005347:Fibroblasts; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D016281:Oncogene Protein gp140(v-fms); D010766:Phosphorylation; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D016186:Receptor, Macrophage Colony-Stimulating Factor; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D016184:Receptors, Colony-Stimulating Factor; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D012191:Retroviridae Proteins / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D003115:Colony-Stimulating Factors; D006023:Glycoproteins; C000715470:MAS1 protein, human; D008565:Membrane Proteins; D016281:Oncogene Protein gp140(v-fms); D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor; D011994:Recombinant Proteins; D012191:Retroviridae Proteins; D016186:Receptor, Macrophage Colony-Stimulating Factor