TRANSFORMING ACTIVITY AND TISSUE TROPISM OF HYBRID RETROVIRAL GENOMESCONTAINING PORTIONS OF THE V-ABL AND V-SRC ONCOGENES

The v-abl and v-src oncogenes encode activated cytoplasmic tyrosine ki nases with considerable sequence similarity. The v-abl oncogene of the Abelson murine leukemia virus exhibits a narrow tissue tropism for tr ansformation, almost exclusively forming pre-B-cell tumors, while the v-src oncogene can induce a variety of sarcomas and other tumors. To l ocalize the determinants of the narrow tropism of the v-abl gene, we g enerated a series of hybrid retroviral genomes containing portions of the v-abl and v-src oncogenes in a Moloney murine leukemia virus backb one. Each virus was tested for transforming activity in NIH3T3 cells; for transforming activity on bone marrow cultures; and for pathogenici ty in newborn mice. Many of the hybrid oncogenes carried by these viru ses exhibited transforming activity, and demonstrate that the SH2 doma in of each oncogene can be utilized by the kinase domain of the other oncogene for that activity. The results further suggest that a portion of the C-terminal region of v-abl is necessary for the pre-B-cell spe cificity of the oncogene.