Jak-STAT pathway is involved in the induction of TNF-beta gene during stimulation by IL-2

Eur J Immunol. 1998 Mar;28(3):805-10. doi: 10.1002/(SICI)1521-4141(199803)28:03<805::AID-IMMU805>3.0.CO;2-G.


IL-2 is the major regulatory cytokine of the immune system. It plays a key role in T cell survival, growth and activation. IL-2 may induce the expression of multiple genes including some cytokine genes. The induction of these genes is triggered by different signal pathways, one of them being the Jak-STAT signal pathway. The genes regulated by this pathway remain to be determined. By studying IL-2-inducible genes, we have confirmed that the TNF-beta gene is one of the immediate early genes activated by IL-2. By analysis of the DNA sequences around 180-300 bases upstream of the transcription initiation point of the mouse TNF-beta gene, we demonstrate that there is a STAT5 binding site which is essential to the inducibility of the TNF-beta gene. Furthermore, in BA/F3 cells co-transfected with the STAT5A gene and IL-2R beta gene, the activation of the TNF-beta gene promoter by IL-2 was greatly promoted, whereas the TNF-beta gene promoter became IL-2-non-inducible if the STAT5A gene was substituted with a dominant negative STAT5A, i.e. a C-terminally truncated mutant. Taken together, our results show that the Jak-STAT signal pathway is involved in induction of the TNF-beta gene in cells stimulated by IL-2.

MeSH terms

  • Animals
  • Binding Sites
  • Cell Line
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation / drug effects
  • Genes, Immediate-Early
  • Interleukin-2 / pharmacology*
  • Lymphotoxin-alpha / genetics*
  • Mice
  • Milk Proteins*
  • Promoter Regions, Genetic
  • Protein-Tyrosine Kinases / physiology
  • STAT5 Transcription Factor
  • Trans-Activators / physiology*
  • Transcription, Genetic


  • DNA-Binding Proteins
  • Interleukin-2
  • Lymphotoxin-alpha
  • Milk Proteins
  • STAT5 Transcription Factor
  • Stat5a protein, mouse
  • Trans-Activators
  • Protein-Tyrosine Kinases