Essential role for IKKgamma/NEMO in TCR-induced IL-2 expression in Jurkat T cells.
The control of IL-2 gene expression in T cells by multiple transcriptional factors has been extensively explored, however, the role of the NF-kappaB signaling pathway in TCR-dependent IL-2 production still remains unclear. In this study, we used a somatic cell genetics approach to address this question. Triggering TCR in mutant Jurkat T cells lacking IKKgamma/NEMO failed to induce IL-2 due to a selective loss in I-kappaB kinase activity, I-kappaBalpha degradation and NF-kappaB DNA-binding activity. The AP-1 and NF-AT binding activities in the IL-2 promoter were comparable between wild-type and mutant T cells. These defects in the mutant cell line were rescued by the reintroduction of exogenous IKKgamma. Taken together, our data demonstrate that IKKgamma plays an essential role in TCR-induced signaling pathways leading to IL-2 expression.
He
Kai-Li
KL
Immunobiology Center, Mount Sinai School of Medicine, Box 1630, One Gustave L. Levy Place, New York, NY 10029, USA.
Ting
Adrian T
AT
D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D051550:I-kappa B Kinase; D007376:Interleukin-2 / Q000378:metabolism*; D019169:Jurkat Cells; D016328:NF-kappa B / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000201:enzymology*
D007376:Interleukin-2; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human