Journal article
Authors list: Knop, J; Wesche, H; Lang, D; Martin, MU
Publication year: 1998
Pages: 3100-3109
Journal: European Journal of Immunology
Volume number: 28
Issue number: 10
ISSN: 0014-2980
Publisher: Wiley
Abstract:
The association and activation of the IL-1 receptor-associated protein kinase (IRAK) to the IL-1 receptor complex is one of the earliest events detectable in IL-1 signal transduction. We generated permanent clones of the murine T cell line EL4 6.1 overexpressing human (h)IRAK to evaluate the role of this kinase in IL-1 signaling. Overexpression of hIRAK enhanced IL-1-stimulated activation of the transcription factor NF kappa B, whereas a truncated form (N-IRAK) specifically inhibited IL-1-dependent NF kappa B activity. In clones stably overexpressing hIRAK a weak constitutive activation of NF kappa B correlated with a low basal IL-2 production which was enhanced in an IL-1-dependent manner. Compared to the parental cell line the dose-response curve of IL-1-induced IL-2 production was shifted in both potency and efficacy. These results demonstrate that IRAK directly triggers NF kappa B-mediated gene expression in EL4 cells. Qualitatively different effects were observed for the IL-1-induced activation of stress-activated protein (SAP) kinases: permanent overexpression of IRAK did not affect the dose dependence but prolonged the kinetics of IL-1-induced activation of SAP kinases, suggesting that this signaling branch may be regulated by distinct mechanisms.