Our findings have shown that the v-sis translational product is functionally equivalent to platelet-derived growth factor (PDGF). Findings that v-sis was able to induce transformation only of cell types responsive to the proliferative action of PDGF demonstrated that the PDGF-like activities of the v-sis translational product were the functions responsible for its transforming ability. We have also shown that transcriptional activation of the normal human v-sis/PDGF-2 gene in cells capable of responding to PDGF leads to morphologic transformation of such cells. We have defined the full extent of the sis transcriptional unit. Promoter signals were identified immediately upstream of the mRNA start site in normal human genomic DNA Identification and isolation of these putative regulatory sequences make it now possible to investigate the biologic consequences of c-sis/PDGF-2 gene transcriptional activation in normal human cells. A survey of human tumor cells for the presence of fgr proto-oncogene mRNA has revealed that expression of this gene is highly restricted. Normal or transformed B-lymphocytes naturally or deliberately infected with Epstein-Barr virus expressed detectable c-fgr mRNA. These and other findings demonstrated for the first time induction of a proto-oncogene in response to infection by a DNA tumor virus. The normal human fgr gene has been isolated. Human fgr DNA clones made it possible to demonstrate that the fgr proto-oncogene is distinct from cellular homologues of other tyrosine kinase-encoding onc genes. The fgr proto-oncogene was localized to the distal portion of the short arm of human chromosome 1 at p36.1 by in situ hybridization. Taken together, our findings establish that the fgr proto-oncogene is a unique member of the tyrosine kinase gene family.
