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

J Immunol. 1992 Jul 1;149(1):83-91.


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.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Compartmentation
  • Cell Nucleus / metabolism
  • Gene Expression
  • Humans
  • In Vitro Techniques
  • Interleukin-2 / physiology*
  • Mice
  • Molecular Sequence Data
  • NF-kappa B / physiology*
  • Oligodeoxyribonucleotides / chemistry
  • Protein Binding
  • Protein-Tyrosine Kinases / metabolism
  • RNA, Messenger / genetics
  • Receptors, Interleukin-2 / chemistry
  • Receptors, Interleukin-2 / physiology*
  • Signal Transduction
  • Structure-Activity Relationship
  • Time Factors
  • Tumor Cells, Cultured


  • Interleukin-2
  • NF-kappa B
  • Oligodeoxyribonucleotides
  • RNA, Messenger
  • Receptors, Interleukin-2
  • Protein-Tyrosine Kinases