Tissue-specific expression and developmental regulation of the human fgr proto-oncogene.

Abstract

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 offgr transcripts were also present in U937 promonocytic cells and increased in abundance with 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced differentiation. The level offgr 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 offgr mRNA was longer than 8 h, these changes are best explained by transient transcriptional activation offgr 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.Of the retrovirus-transforming genes described to date, nearly half encode proteins that possess protein-tyrosine kinase activity or share structural homology with genes specifying such enzymes. Recent discoveries have shown that at least three of these tyrosine kinases are altered versions of cell surface receptors for polypeptide growth factors (8,22,29). However, the protein tyrosine kinase specified by src (32) and the src-related products of abl (1), lck (20, 33), fyn (16,26), and hck (24, 37) proto-oncogenes do not contain hydrophobic stretches capable of spanning the plasma membrane and therefore lack extracellular ligandbinding domains. Such evidence has suggested that not all oncogene-encoded tyrosine kinases represent receptors for growth-promoting polypeptides.A striking degree of amino acid sequence homology sharply delimits protein tyrosine kinases specified by retrovirus onc genes. The src gene family of oncogenes includes v-src, v-yes, and v-fgr, all of which are at least 75% identical to one another in amino acid sequence within their catalytic domains (13,14,17,21,32). The normal cellular counterparts of v-src and v-yes genes appear to be expressed in a wide range of normal and transformed cells (21, 27), whereas expression of the fgr proto-oncogene is more limited (3, 35). Transcripts of the fgr proto-oncogene have been found in both normal and malignant B lymphocytes infected with Epstein-Barr virus as well as an unknown component o...

Fgr Expression Restricted to Subpopulation of Monocyte/Macrophage Lineage in Resting Conditions Is Induced in Various Hematopoietic Cells after Activation or Transformation

“…The expression of Fgr has been extensively studied in humans using normal blood leukocytes and myelomonocytic leukemia cells (28,29,32). In these studies, the expression of c-fgr mRNA in a myelomonocytic lineage was increased with development/maturation.…”

Increased pathology in lungs of mice after infection with an α-crystallin mutant of Mycobacterium tuberculosis: changes in cathepsin proteases and certain cytokines

“…CatG is highly abundant in the azurophilic granules of neutrophils and monocytes (Senior & Campbell, 1984;Senior et al, 1982), and is synthesized during the promyelocytic and promonocytic stages of maturation, respectively (Bainton et al, 1971;van der Meer et al, 1981). In U937 monocytes, treatment with the phorbol ester 12-Otetradecanoylphorbol 13-acetate (TPA) results in transcriptional downregulation of catG (Hanson et al, 1990;Ley et al, 1989;Welgus et al, 1986). Since there is no evidence that catG is expressed by alveolar epithelial pneumocytes, it is possible that the CatG detected in the normal lung is derived from circulating monocytes and/or neutrophils.…”

Thrombin-dependent association of phosphatidylinositol-3 kinase with p60c-src and p59fyn in human platelets.

“…In a search for other protein-tyrosine kinases expressed in platelets, we took advantage of our specific antipeptide sera directed against p55c-fgr and p59fn, both members of the src family of nonreceptor tyrosine * Corresponding author. kinases known to be expressed in hematopoietic cells (7,11,12).…”