Activation of the feline c-fms proto-oncogene: multiple alterations are required to generate a fully transformed phenotype.
The v-fms oncogene is capable of producing tumors in vivo and transforming cells in culture; in contrast, the c-fms proto-oncogene is nontransforming. In this report we present the complete nucleotide sequence of a feline c-fms cDNA, the progenitor of the v-fms oncogene. Comparison of this sequence with that of v-fms shows that the proteins encoded by these two genes differ by nine amino acid substitutions and the replacement of 50 C-terminal amino acids present in c-fms by 11 unrelated residues in v-fms. Using chimeric fms genes and site-directed mutagenesis, we have determined that the C-terminal modification present in v-fms is sufficient to generate a partially transforming phenotype, but that mutations at amino acid positions 301 and 374 are required (in addition to the C-terminal modification) to generate a fully transforming fms gene.
Woolford
J
J
Department of Cell Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
McAuliffe
A
A
Rohrschneider
L R
LR
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002415:Cats; D004247:DNA / Q000032:analysis; D005786:Gene Expression Regulation; D005256:Leukemia Virus, Feline / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis
D012333:RNA, Messenger; D004247:DNA