Transforming activity and tissue tropism of hybrid retroviral genomes containing portions of the v-abl and v-src oncogenes.
The v-abl and v-src oncogenes encode activated cytoplasmic tyrosine kinases with considerable sequence similarity. The v-abl oncogene of the Abelson murine leukemia virus exhibits a narrow tissue tropism for transformation, almost exclusively forming pre-B-cell tumors, while the v-src oncogene can induce a variety of sarcomas and other tumors. To localize the determinants of the narrow tropism of the v-abl gene, we generated a series of hybrid retroviral genomes containing portions of the v-abl and v-src oncogenes in a Moloney murine leukemia virus backbone. Each virus was tested for transforming activity in NIH3T3 cells; for transforming activity on bone marrow cultures; and for pathogenicity in newborn mice. Many of the hybrid oncogenes carried by these viruses exhibited transforming activity, and demonstrate that the SH2 domain 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 specificity of the oncogene.
Hevezi
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P
Department of Microbiology, Columbia University, New York, New York 10032.
Alin
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K
Goff
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SP
D016475:3T3 Cells; D000818:Animals; D000831:Animals, Newborn; D001854:Bone Marrow Cells; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D004274:DNA, Recombinant; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D016313:Genes, abl; D016391:Genes, src; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012190:Retroviridae / Q000235:genetics
D004274:DNA, Recombinant; D011993:Recombinant Fusion Proteins