Isolation and characterization of murine fra-1: induction mediated by CD40 and surface Ig is protein kinase C dependent.
The murine fra-1 gene, encoding Fos-related Ag 1, was isolated from a splenic cDNA library and sequenced. Murine fra-1 was highly homologous to rat and human fra-1. Oligonucleotide primers based on the murine sequence were used to construct a quantitative reverse transcription-PCR assay for gene expression. B lymphocyte stimulation via both CD40 and surface Ig (sIg) receptors substantially induced fra-1 expression, and for both receptors, induction was protein kinase C (PKC) dependent. This contrasts with induction of c-fos by both CD40 and sIg, which is PKC independent and indicates that CD40 is capable of signaling through PKC or a closely related kinase. Induction of fra-1 following engagement of CD40 did not require protein synthesis, suggesting that the PKC-dependent linkage between CD40 and fra-1 is direct. CD40-mediated fra-1 induction did require tyrosine kinase activity. These results demonstrate that CD40, like sIg, may employ PKC in producing select outcomes, that individual B cell receptors may signal downstream events via both PKC-dependent and PKC-independent pathways, and that multiple signal transduction pathways may be used to activate the expression of closely related genes.
Department of Medicine, Boston University Medical Center, MA 02118, USA.
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D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand; D018076:DNA, Complementary / Q000235:genetics; D015723:Gene Library; D005796:Genes; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice / Q000235:genetics*; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics*; D051381:Rats; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*; D013045:Species Specificity; D000099169:Fos-Related Antigen 1
D019013:CD40 Antigens; D023201:CD40 Ligand; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D011493:Protein Kinase C; D011505:Protein-Tyrosine Kinases; D016760:Proto-Oncogene Proteins c-fos; D011947:Receptors, Antigen, B-Cell; D000099169:Fos-Related Antigen 1