The GR-FeSV onc gene, v-fgr, appear to have arisen as a result of a recombinational event involving genes coding for actin and a tyrosine-specific protein kinase. In an effort to understand the role of the actin domain in transformation, a series of mutant GR-FeSVs with successive deletions in their gag and/or actin domains were constructed and tested for their ability to transform NIH/3T3 cells in a transfection assay. Preliminary data suggest that the actin sequence has little effect on transforming activity in vitro. The human fgr proto-oncogene has been isolated and characterized and shown to be a distinct sequence located on the short arm of chromosome 1. Furthermore, it has been shown that the fgr proto-oncogene is evolutionarily conserved and is distinct from other related proto-oncogenes which encode proteins that are as much as 80% related in amino acid sequence. These findings strongly imply evolutionary pressure to conserve similar structure and kinase function at different human loci. A survey of human tumor cell lines and normal tissues was conducted for evidence of fgr proto-oncogene expression. Wide distribution of a single fgr-related mRNA species of 3 kb was found in lymphoproliferative disorders and neurologic tumors but limited expression in carcinomas and sarcomas. Further scrutiny of the data revealed that expression of c-fgr was associated with Epstein-Barr virus (EBV) genome-positive Burkitt's lymphoma lines. Additional experiments have shown that the immortalization function of EBV may involve activation of c-fgr, a member of the tyrosine kinase gene family.
