Activation of the Cellular src Gene by Transducing Retrovirus

Abstract

Newly isolated strains of avian sarcoma virus, S1 and S2, were shown to have the transduced cellular src gene as their viral transforming gene (Yamagishi et al., Virology 137:266–275, 1984). In this work, the S1 and S2 genomes were molecularly cloned, and the junction sequences between the viral genomes and the c-src genes and the complete nucleotide sequences of the v-src genes transduced in these viruses were determined. Data on the junction sequences suggested that 5′ recombination had occurred between the 5′-noncoding region of c-src and the 5′ region of the gag sequence encoding p19 in both viruses and that 3′ recombination had occurred in the last coding exon of c-src with either the middle portion of the env sequence encoding gp85 for S1 or the 3′ portion of pol coding for reverse transcriptase for S2. Comparison of the amino acid sequences of the S1 and S2 src products deduced from the nucleotide sequences (pp62^S1-src and pp62^S2-src with that of c-src protein (pp60^c-src) indicated that in pp62^S1-src the 8 carboxy-terminal amino acid residues of the total of 533 in pp60^c-src are replaced by 43 residues translated from the env sequence at the wrong frame. In pp62^S2-src, on the other hand, the 14 carboxy-terminal amino acids of pp60^c-src are replaced by the 38 carboxy-terminal residues of reverse transcriptase. The mechanism of c-src transduction and the structural changes necessary for pp60^c-src activation are discussed.