The transforming protein of a primate sarcoma virus and a platelet-derived growth factor are derived from the same or closely related cellular genes. This conclusion is based on the demonstration of extensive sequence similarity between the transforming protein derived from the simian sarcoma virus onc gene, v-sis, and a human platelet-derived growth factor. The mechanism by which v-sis transforms cells could involve the constitutive expression of a protein with functions similar or identical to those of a factor active transiently during normal cell growth.

The predicted amino acid sequence of the simian sarcoma virus (SSV) transforming gene product, p28sis, closely corresponds to that of human platelet-derived growth factor (PDGF). We demonstrate that p28sis rapidly undergoes a series of discrete processing steps including dimer formation and proteolytic digestion to yield molecules structurally and immunologically resembling biologically active PDGF.

The only known product of the Snyder-Theilen strain of feline sarcoma virus (ST-FeSV) is a 85,000-dalton protein, designated ST P85, that contains feline leukemia virus gag gene encoded proteins (p15, p12, and a fragment of p30) and a sarcoma virus-specific polypeptide. Antibodies directed against the latter immunoprecipitated a 92,000-dalton phosphoprotein (NCP 92) expressed at low levels in normal feline embryo fibroblasts as well as in feline cells of epithelial or lymphoid origin. Normal cellular proteins crossreactive with ST P85 were also detected in cell lines from various other mammalian species. These results suggest that the ST-FeSV sequences encoding for the sarcoma virus-specific domain of ST P85 originated from an evolutionarily conserved cellular gene expressed in cells of independent differentiation lineage. Immunoprecipitates containing ST-FeSV P85 exhibited a protein kinase activity that specifically phosphorylated tyrosine residues. The physiological significance of this finding is illustrated by the finding that phosphotyrosine is an intrinsic component of ST

The complete nucleotide sequence ofthe proviral genome of simian sarcoma virus (SSV), an acute transforming retrovirus of primate origin, has been determined. Like

The integrated form of simian sarcoma virus (SSV) was molecularly cloned in the Charon 16A strain of bacteriophage A. In transfection analysis, the recombinant viral DNAs demonstrated the ability to transform cells in tissue culture at high efficiency. Such transformants possessed typical SSV morphology, expressed simian sarcoma associated virus (SSAV) gag gene products in the absence of virus release, and released SSV after superinfection with a type C helper virus. A physical map ofthe 5.8-kilobase-pair (kbp) recombinant viral DNA clone, deduced from restriction endonuclease analysis, revealed a 5. 1-kbp SSV genome containing 0.55-kbp-long terminal repeats flanked by 0.45 and 0.25 kbp ofcontiguous host cell sequences. By R-loop analysis, the viral DNA molecule contained two regions of homology to SSAV, separated by a 1.0-kbp nonhomologous region. This SSV-specific sequence was shown to be uniquely represented within the normal cellular DNA of diverse mammalian species, including human. Our results demonstrate that this primate transforming retrovirus arose in nature by recombination of a type C helper virus and a host cellular gene.