IL-2-induced signal transduction involves the activation of nuclear NF- kappa B expression

• Published in: The Journal of immunology (1950) Vol. 149; no. 1; pp. 83 - 91
• Main Authors: Arima, N, Kuziel, WA, Grdina, TA, Greene, WC
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 01.07.1992; American Association of Immunologists
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Animals; Base Sequence; Biological and medical sciences; Cell Compartmentation; Cell Nucleus - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression; Humans; Immunobiology; In Vitro Techniques; Interleukin-2 - physiology; Lymphokines, interleukins ( function, expression); Mice; Molecular Sequence Data; NF-kappa B - physiology; Oligodeoxyribonucleotides - chemistry; Protein Binding; Protein-Tyrosine Kinases - metabolism; Receptors, Interleukin-2 - chemistry; Receptors, Interleukin-2 - physiology; Regulatory factors and their cellular receptors; RNA, Messenger - genetics; Signal Transduction; Structure-Activity Relationship; Time Factors; Tumor Cells, Cultured; Human; Rodentia; Cytokine; Activation; Signal transduction; Immunogenetics; Vertebrata; Mammalia; Cell line; Interleukin 2; Mouse; T-Lymphocyte; Second messenger
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.149.1.83

Using electrophoretic mobility shift assays and DNA-protein cross-linking techniques, we demonstrate that IL-2 binding to functional forms of the human IL-2R activates nuclear expression of the eukaryotic transcription factor NF-kappa B. These inductive effects of IL-2 were observed in three different cellular systems including human Jurkat T cells stably transfected with IL-2R beta cDNA, mouse pro-B BA/F3 cells stably expressing human IL-2R beta chains either alone or in combination with human or murine IL-2R alpha chains, and purified primary resting human T cells constitutively displaying small numbers of IL-2R beta molecules. IL-2 activation of nuclear NF-kappa B expression is regulated in part at a post-translational level, involving the rapid translocation of both the 50- and 65-kDa subunits of NF-kappa B from the cytoplasm to the nucleus. However, IL-2 induction also produced an increase in mRNA for NF-kappa B p105, indicating an additional pretranslational component of regulation. In contrast, IL-2 exerts only minor effects on NF-kappa B p65 mRNA expression. IL-2 induction of NF-kappa B through the IL-2R beta subunit was both correlated with activation of the endogenous IL-2R alpha gene and critically dependent upon the presence of a serine-rich cytoplasmic domain within IL-2R beta (amino acid residues 267-312). This domain has previously been shown to be essential for IL-2-induced cell growth and may correspond to a binding site for an IL-2R beta-associated tyrosine kinase. Together, these findings suggest that NF-kappa B may play an important role as one intracellular second messenger relaying signals from the plasma membrane to cell nucleus that leads to IL-2-induced activation and growth.