Isolation of v-fms and its human cellular homolog

Abstract

The integrated form of McDonough FeSV proviral DNA, including cellular flanking sequences, was molecularly cloned from nonproductively transformed Fisher rat cells. Acquired cellular-derived (v-fms) sequences within the cloned proviral DNA were mapped from between 2.6 and 5.5 kb from the 5'LTR. Upon transfection, the cloned proviral DNA was biologically active; it caused induction of the transformed phenotype and the resulting transformed cells expressed the major McDonough FeSV translational product, P170gag-fms at high level. Using a series of molecular probes representing subgenomic regions of the viral v-fms gene, a cosmid library of human lung carcinoma DNA was screened for v-fms homologous sequences. Three cosmid clones containing overlapping v-fms homologous cellular DNA inserts, representing a contiguous region of cellular DNA sequence of approximately 64 kb in length, were isolated. Within this region of human genomic DNA, v-fms homologous sequences are dispersed over a total region of around 32 kb. These represent the entire human cellular homolog of v-fms, are colinear with the viral v-fms transforming gene, and contain a minimum of four intervening sequences. At least 12 regions of highly repetitive DNA sequences have been mapped in close proximity to c-fms coding sequences.