Avian sarcoma viruses, protein kinases and cell transformation.

Abstract

The first RNA tumour virus to be isolated and identified as such was the Rous sarcoma virus (RSV), which causes the transformation of cells in culture as well as fibrosarcomas when injected into suitable host animals (for reviews see Hanafusa (1977) and Bishop (1978)). The genome of RSV has been studied intensively for the past 10-12 years, and it has been shown that the virus itself carries a gene responsible for malignant transformation. This gene, denotedsrcfor sarcoma, was identified genetically through the isolation of temperature-sensitive mutants that were conditional for cell transformation in culture. These mutants are able to transform cells at a temperature of 35 °C, the permissive temperature, but are unable to transform cells morphologically at 41 °C, the non-permissive temperature. The existence of such temperature sensitive mutants implied that the product of the viral transforming gene, in RSV, was a protein (Kawai & Hanafusa 1971). In addition to temperature-sensitive mutants, non-conditional mutants were isolated that had deletions of the src gene. These mutants are unable to transform cells in culture or to cause fibrosarcomas under most conditions. About 4 years ago, the product of the src gene was identified as a phosphoprotein (Mt= 60000); this protein was denoted pp60src(Purchioet al.1978). The RSV genome and the expression of the src gene is illustrated in figure 1.