Jak-STAT pathway is involved in the induction of TNF-beta gene during stimulation by IL-2.
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.
Lu
L
L
Shanghai Institute of Biochemistry, Chinese Academy of Sciences, China.
Zhu
J
J
Zheng
Z
Z
Yan
M
M
Xu
W
W
Sun
L
L
Theze
J
J
Liu
X
X
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D017781:Genes, Immediate-Early; D007376:Interleukin-2 / Q000494:pharmacology*; D008233:Lymphotoxin-alpha / Q000235:genetics*; D051379:Mice; D008894:Milk Proteins; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000502:physiology*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D008233:Lymphotoxin-alpha; D008894:Milk Proteins; D050799:STAT5 Transcription Factor; C494093:Stat5a protein, mouse; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases