Tissue-specific expression and developmental regulation of the human fgr proto-oncogene.
In this study, we show that c-fgr proto-oncogene 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. 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 splicing of intron 7 appeared to occur after the splicing of most of the other introns; partially spliced molecules containing intron 7 did not appear to be transported into the cytoplasm. Very low levels of fgr transcripts were also present in U937 promonocytic cells and increased in abundance with 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced differentiation. The level of fgr transcripts began to increase 2 to 4 h after TPA addition, peaked at 8 h, and subsequently declined. Since we found that the half-life of fgr mRNA was longer than 8 h, these changes are best explained by transient transcriptional activation of fgr during TPA-induced differentiation, although nuclear runoff experiments were not sensitive enough to detect this event. Cycloheximide also caused accumulation of c-fgr transcripts in U937 cells; no superinduction was observed when TPA and cycloheximide were added at the same time. Induction by either agent was blocked with actinomycin D. These results demonstrate that the c-fgr gene is expressed in a tissue- and development-specific fashion and suggest that constitutive expression of c-fgr in U937 cells is regulated by a labile transcriptional repressor.
Ley
T J
TJ
Department of Medicine, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri 63110.
Connolly
N L
NL
Katamine
S
S
Cheah
M S
MS
Senior
R M
RM
Robbins
K C
KC
D004720:Endonucleases; D005786:Gene Expression Regulation; D006098:Granulocytes / Q000032:analysis*; D006801:Humans; D007438:Introns; D008264:Macrophages / Q000032:analysis*; D009000:Monocytes / Q000032:analysis*; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D015347:RNA Probes; D012326:RNA Splicing; D012333:RNA, Messenger / Q000032:analysis; D015719:Single-Strand Specific DNA and RNA Endonucleases; D014158:Transcription, Genetic
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D015347:RNA Probes; D012333:RNA, Messenger; D004720:Endonucleases; D015719:Single-Strand Specific DNA and RNA Endonucleases