Receptor-specific induction of individual AP-1 components in B lymphocytes.
The inducible nuclear transcription factor complex, AP-1, typically consists of heterodimers between Jun and Fos proteins. Although components are drawn from families of related molecules, little is known about the physiologic regulation of jun- and fos-related gene products. In particular, it is not known whether expression of individual family members is stimulus-specific or whether the same signaling pathways are responsible for induction of all subunits. To clarify these issues, AP-1 components were examined following activation of primary B lymphocytes through two separate receptors, the surface Ig Ag receptor, and the CD40 receptor for T cell influences. Both forms of stimulation led to expression of JunB and JunD mRNA and protein; however, induction of JunB mediated by anti-Ig Ab was protein kinase C (PKC)-dependent, whereas induction mediated by CD40 ligand was resistant to PKC depletion. The two forms of stimulation diverged even further with respect to Fos expression. Although both stimuli induced c-Fos, expression of FosB was stimulus specific at both the mRNA and protein levels, in that this component was induced by anti-Ig but not by CD40 ligand. Stimulated expression of c-Fos and FosB was in all cases PKC-independent. These results provide evidence for receptor-specific differences in the expression of AP-1 components, primarily with respect to FosB. They also indicate that separate intracellular pathways may be used for induction of jun and fos gene products and that the same transcription factor (junB) may be triggered by two surface receptors through separate pathways that differ in PKC dependence.
Huo
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Department of Medicine, Boston University Medical Center, MA 02118.
Rothstein
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D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D015153:Blotting, Western; D019013:CD40 Antigens; D023201:CD40 Ligand; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D018808:Transcription Factor AP-1 / Q000096:biosynthesis*
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011947:Receptors, Antigen, B-Cell; D018808:Transcription Factor AP-1; D023201:CD40 Ligand; D011493:Protein Kinase C