FGR, Active

Fgr is a protooncogene that is a unique member of the tyrosine kinase gene family. It is localized to the distal portion of the short arm of human chromosome 1 at p36.1-36.2 by in situ hybridization (1). Certain lymphomas (but not sarcomas or carcinomas) express fgr-related messenger RNA. This transcript is detected in Burkitt's lymphoma cell lines naturally infected with Epstein-Barr virus (EBV), but not in EBV-negative Burkitt's lymphoma cells (2). Normal umbilical cord or peripheral blood lymphocyte lines established in vitro by EBV infection also contain detectable c-fgr mRNA. Moreover, a 50-fold increase of the steady-state c-fgr mRNA concentration is observed when uninfected Burkitt's lymphoma cell lines are deliberately infected with EBV demonstrating the induction of a proto-oncogene in response to infection by a DNA tumour virus. Fgr expression is limited to normal peripheral blood granulocytes, monocytes, and alveolar macrophages, all of which contain 50 to 100 copies of c-fgr mRNA per cell (3). The c-fgr RNA molecules in these cells consisted of partially spliced transcripts containing intron 7 and completely spliced molecules capable of encoding the predicted p55 c-fgr protein. The level of fgr transcripts begin to increase 2 to 4 h after TPA addition, peak at 8 h, and subsequently declined suggesting transient transcriptional activation of fgr during TPA-induced differentiation. Cycloheximide also causes accumulation of c-fgr transcripts in U937 cells. Thus, c-fgr gene is expressed in a tissue- and development-specific fashion and constitutive expression of c-fgr in U937 cells is regulated by a labile transcriptional repressor.