A mutation at the major phosphotyrosine in pp60v-src alters oncogenic potential.

Previously (M.A. Snyder, J.M. Bishop, W.W. Colby, and A.D. Levinson, 1983, Cell 32, 891-901) a mutant was constructed in v-src in which the major phosphotyrosine site, tyr-416, was converted to phenylalanine. This mutant has now been examined both for tumorigenicity and a number of in vitro parameters relating to the transformed state and to the known properties of pp60v-src, the product of v-src. Mouse cells transformed by this mutant gene, which are called RSV-SF1, are tumorigenic only if tested in immunodeficient mice, whereas cells transformed by the wild-type parent are tumorigenic in either syngeneic or immunodeficient animals. When examined in vitro, RSV-SF1-transformed cells are virtually indistinguishable from cells transformed by wild-type pp60v-src. These findings raise the possibility that the protein kinase activity of pp60v-src may not be fully responsible for tumorigenesis by v-src, and moreover suggest that evasion of the host immune response is a necessary step in tumorigenesis by v-src.