A dominant suppressive mutation in a cellular gene restores the nontransformed phenotype to v-fms-transformed mink cells.

A nontransformed revertant subclone (GVR17) was isolated from mutagen-treated populations of mink epithelial cells which had been transformed by the Susan McDonough strain of feline sarcoma virus (SM-FeSV). The revertant cells, although contact-inhibited for growth and unable to form colonies in semisolid medium, contained two copies of integrated SM-FeSV proviral DNA, expressed high levels of the v-fms oncogene product and its associated tyrosine kinase activity, and yielded rescuable viruses able to transform parental mink epithelial and mouse NIH3T3 cells. The transformed phenotype was suppressed in cell hybrids generated by fusing revertant and v-fms-transformed mink cells, indicating that GVR17 cells harbored a dominant cellular mutation that inhibited transformation by the v-fms oncogene. The revertant cells were refractory to retransformation by retroviruses containing v-fms or v-abl oncogenes, but could be transformed by v-ras-, v-raf-, and v-fes-containing retroviruses. Thus, the suppressing activity in GVR17 cells discriminates between transforming signals mediated by different tyrosine kinases and fails to block the transforming activity of two oncoproteins exhibiting either GTP-binding or serine/threonine kinase activity.