"Replacement" of COOH-terminal truncation of v-fms with c-fms sequences markedly reduces transformation potential.
Protooncogenes when transduced by retroviruses may undergo structural modifications that render their gene products oncogenic. The c-fms gene encodes a transmembrane protein with tyrosine kinase activity that is very similar or identical to the receptor for the monocyte-macrophage colony-stimulating factor. Its transforming homologue (v-fms) in the Susan McDonough strain feline sarcoma virus causes fibrosarcomas in cats. Molecular cloning and sequence analysis of the cDNA that encodes the cytoplasmic domain of the human c-fms gene shows that the product of the transduced viral homologue, v-fms, is truncated at the COOH-terminal end. The COOH-terminal 40 amino acids of the c-fms gene product are replaced in the v-fms gene product by 11 amino acids encoded by the retroviral genome. Hybrid v-fms/c-fms genes, in which either the entire cytoplasmic domain or the COOH-terminal coding sequences of the v-fms gene were replaced by the corresponding segments of the c-fms gene, had a reduced ability to transform fibroblasts despite a high level of encoded protein on the cell surface. These data indicate that the COOH-terminal modifications contribute to the transforming potential of the v-fms viral oncogene product.
D000595:Amino Acid Sequence; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004247:DNA / Q000302:isolation & purification; D066246:ErbB Receptors / Q000032:analysis; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009856:Oncogene Proteins, Viral / Q000032:analysis*; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D013329:Structure-Activity Relationship; D014161:Transduction, Genetic
D009856:Oncogene Proteins, Viral; D011518:Proto-Oncogene Proteins; D004247:DNA; D066246:ErbB Receptors