Structure and expression of c-fgr protooncogene mRNA in Epstein-Barr virus converted cell lines

Abstract

Summary The c-fgr protooncogene is a member of the c-src family of tyrosine kinases. Expression of c-fgr was studied in a series of Epstein-Barr virus (EBV) negative Burkitt's lymphoma cell lines and their EBVconverted derivatives. Two transcripts, of 2.9kb and 3.5kb, were present at dramatically elevated levels following EBV-conversion.The structure of the c-fgr transcripts was studied by the isolation and nucleotide sequence analysis of cDNA clones. This indicated that the c-fgr protein encoded by the mature mRNA would contain 529 amino acids and have a molecular weight of approximately 58,000. The N-terminus of the predicted c-fgr protein has low amino acid homology with the N-termini of other members of this family of proteins, suggesting a cell specific function for the N-terminal domain. Analysis of the c-fgr cDNA clones also revealed the presence of alternative functional polyadenylation signals, although the use of these does not account for the size difference between the two major c-fgr transcripts.

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

“…Actually, fgr mRNA was abundantly detected in terminally differentiated cells, such as normal circulating granulocytes and tissue macrophages. Fgr molecules were shown to be expressed also in EBV-infected B lymphocytes (7, 28) with a unique 5'-untranslated region which was not utilized in a myelomonocytic cell line (4,19). Further, the expression of c-fgr mRNA in the EBVinfected B cells appeared to be operated by the differential promoter utilization and alternative splicing (7).…”

Regulation of C‐FGR proto‐oncogene expression in epstein‐barr virus infected B‐cell lines

“…pFal is a human c-fgr cDNA clone with an insert of 2156bp, extending from nucleotide 37 of the c-jgr coding region to nucleotide 607 of the 3' untranslated region. A restriction map of pFal, with its nucleotide sequence, has been published (Brickell and Patel, 1988). pCAl is an 800bp BglII-EcoRI genomic fragment encompassing the human immunoglobulin A light chain CAl constant region exon, cloned into pBR322 (Taub et al, 1983).…”

“…Fgr is a member of the Src family of cytoplasmic protein tyrosine kinases, which also includes Fyn, Hck, Lck, Lyn, Tkl and Yes. These proteins are thought to be involved in intracellular signalling during the growth and differentiation of different cell types (Brickell and Patel, 1988). Fgr is expressed in mature peripheral blood monocytes and granulocytes, and in alveolar and splenic macrophages (Ley et al, 1989).…”

“…A role for Fgr in the EBV-induced immortalization of Blymphocytes has been suggested by the observation that c-jgr mRNA levels, which are low in EBV-negative BL cell lines, are considerably elevated following EBV conversion of EBVnegative BL cell lines (Brickell and Patel, 1988;Klein et al, 1988;Cheah et al, 1986) with the B95-8 strain of EBV. EBVpositive BL biopsies and cell lines also express elevated levels of c-fgr mRNA.…”

The <i>c-fgr</i>Proto-Oncogene: Expression in Epstein-Barr-Virus-Infected B Lymphocytes and in Cells of the Myelomonocytic and Granulocytic Lineages

“…1]. In humans, the c-fgr gene is located at chromosome 1 p36.2-p36.1 [2], and genomic clones [3] and human [4][5][6] and murine [7,8] cDNA clones have been isolated. Nucleotide sequence analysis of these clones has shown that c-fgr is a member of a gene family which also includes c-src, fyn, hck, lek, lyn and c-yes [reviewed in ref .…”