title: A point mutation in the extracellular domain of the human CSF-1 receptor (c-fms proto-oncogene product) activates its transforming potential.
abstract: A human CSF-1 receptor containing an "activating" mutation in its extracellular domain (serine for leucine 301) induced morphologic transformation, anchorage-independent growth, and tumorigenicity in mouse NIH 3T3 cells. A second regulatory mutation within the receptor's intracytoplasmic carboxy-terminal tail (phenylalanine for tyrosine 969) augmented transforming efficiency but was itself insufficient to induce transformation. Like the v-fms oncogene product, receptors bearing the activating mutation retained high-affinity binding sites for CSF-1 but were retarded in transport to the cell surface and were phosphorylated on tyrosine in the absence of ligand. Although the activating mutation does not affect the CSF-1 binding site in the receptor extracellular domain, it must induce a conformational change that mimics the effect of ligand binding, resulting in CSF-1-independent signals for cell growth.
authors.affiliation: Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: M F
authors.initials: MF
authors.lastname: Roussel
authors.forename: J R
authors.initials: JR
authors.lastname: Downing
authors.forename: C W
authors.initials: CW
authors.lastname: Rettenmier
authors.forename: C J
authors.initials: CJ
authors.lastname: Sherr
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000378:metabolism; D006801:Humans; D051379:Mice; D009154:Mutation; D010649:Phenylalanine; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011519:Proto-Oncogenes; D016186:Receptor, Macrophage Colony-Stimulating Factor; D014443:Tyrosine
chemical_list: D003115:Colony-Stimulating Factors; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D014443:Tyrosine; D010649:Phenylalanine; D016186:Receptor, Macrophage Colony-Stimulating Factor