title: NF-kappa B/Rel participation in the lymphokine-dependent proliferation of T lymphoid cells.
abstract: Proliferative responses of lymphoid cells to IL-2 and IL-4 depend on activation of the cells, but the mechanism(s) by which activation enhances cellular competence to respond to cytokines is not fully understood. The NF-kappaB/Rel family represents one signal transduction pathway induced during such activation. We show in this study that inhibition of NF-kappaB through the expression of an IkappaBalpha (inhibitory protein that dissociates from NF-kappaB) mutant refractory to signal-induced degradation (IkappaBalpha(DeltaN)) interfered with the acquisition of competence to proliferate in response to IL-4 as well as IL-2. Thymocytes and T cells from IkappaBalpha(DeltaN) transgenic mice expressed normal levels of IL-2R subunits. However, transgenic cells exhibited a dramatic defect in Stat5A activation treatment with IL-2, and a similar defect was observed for IL-4-induced Stat5. In contrast, T lymphoid cells with inhibition of NF-kappaB showed normal insulin receptor substrate-2 phosphorylation and only a modest decrease in Stat6 activation and insulin receptor substrate-1 phosphorylation after IL-4 stimulation. These results indicate that the NF-kappaB/Rel/IkappaBalpha system can regulate cytokine receptor capacitation through effects on the induction of downstream signaling by the Stat transcription factor family.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University Medical School, Nashville, TN 37232, USA.
authors.forename: A
authors.initials: A
authors.lastname: Mora
authors.forename: J
authors.initials: J
authors.lastname: Youn
authors.forename: A
authors.initials: A
authors.lastname: Keegan
authors.forename: M
authors.initials: M
authors.lastname: Boothby
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D020672:I-kappa B Proteins; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008222:Lymphokines / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008894:Milk Proteins; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D020569:Proto-Oncogene Proteins c-rel / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D019948:Receptors, Interleukin-4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D019076:Transgenes / Q000276:immunology
chemical_list: D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D008222:Lymphokines; D008894:Milk Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D020569:Proto-Oncogene Proteins c-rel; D015375:Receptors, Interleukin-2; D019948:Receptors, Interleukin-4; D050799:STAT5 Transcription Factor; C494093:Stat5a protein, mouse; D015534:Trans-Activators; D000072000:NF-KappaB Inhibitor alpha; D015847:Interleukin-4