Fibroblast and hematopoietic cell transformation by the fms oncogene (CSF-1 receptor).
The c-fms proto-oncogene encodes the receptor for the mononuclear phagocyte colony stimulating factor, CSF-1. Although the tyrosine kinase activity of the CSF-1 receptor is stimulated by its ligand, the viral oncogene, v-fms, encodes a constitutive receptor kinase that can transform both fibroblasts and hematopoietic cells by a nonautocrine mechanism. Mutations in the c-fms gene as well as a critical alteration of the distal 3' coding sequences appear to be responsible for fully activating its latent transforming potential. The v-fms gene can convert CSF-1 or IL-3 dependent hematopoietic cell lines to factor independence and render them tumorigenic. Expression of the v-fms gene product does not transmodulate the normal receptors for CSF-1 or IL-3 and affects neither their affinity, number, nor potential to be independently down-regulated by their ligands or by phorbol esters. The ability of v-fms to transform hematopoietic target cells suggests that critical alterations in the c-fms proto-oncogene might similarly contribute to leukemia.
Sherr
C J
CJ
Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
D000595:Amino Acid Sequence; D002472:Cell Transformation, Viral; D003115:Colony-Stimulating Factors / Q000235:genetics*; D005347:Fibroblasts / Q000648:ultrastructure; D005815:Genetic Code; D006412:Hematopoietic Stem Cells / Q000648:ultrastructure; D006801:Humans; D008024:Ligands; D009154:Mutation; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D011956:Receptors, Cell Surface / Q000235:genetics*; D016184:Receptors, Colony-Stimulating Factor; D012689:Sequence Homology, Nucleic Acid
D003115:Colony-Stimulating Factors; D008024:Ligands; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor