The raf Oncogene

Abstract

v-raf is the oncogene of 3611 MSV and was isolated from mouse cells by transduction with murine leukemia virus (MuLV). v-raf is a new member of the src family of oncogenes and has associated ser/thr specific protein kinase activity. The active cellular homolog, c-raf-1, maps on chromosome 6 in the mouse and on chromosome 3p25 in man. There is a second gene in man, c-raf-2, which is an inactive pseudogene. the v-raf as well as the c-raf coded proteins are located predominantly in the cytoplasm. The active human gene, c-raf-1, has a complex structure with 15 exons, 9 of which are homologous to v-raf. An avian carcinoma virus, MH2, transduces the avian homologue of v-raf, v-mil, in addition to a second oncogene, v-myc. v-mil shares sequences with 11 exons of c-raf-1. A 3’ portion of c-raf-1 containing six of the seven amino acid differences relative to v-raf can substitute for 3’ portion of v-raf in a transformation assay. Sequence homologies between c-raf-1 and Moloney leukemia virus at both ends of v-raf indicate that the viral gene was acquired by homologous recombination, probably at the DNA level.