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• W2134246525 abstract "NF-kappa B transcription factors play an important role in the activation of the IL-2 gene in response to TCR ligation. The release of NF-kappa B factors to the nucleus requires phosphorylation and degradation of the inhibitory kappa-B proteins (I kappa Bs). I kappa B alpha and I kappa B beta phosphorylation is dependent on dual signaling by the TCR and the CD28 accessory receptor. This pathway involves a multisubunit I kappa B kinase (IKK) complex, which includes the IKK alpha (IKK-1) and IKK beta (IKK-2) kinases. We demonstrate that stimulation of primary human CD4+ T cells by CD3/CD28 activates two distinct endogenous IKK complexes, a heterodimeric IKK alpha/beta and a homodimeric IKK beta complex. IKK beta overexpression in a Jurkat cell line resulted in the formation of a constitutively active IKK complex, which was CD3/CD28 inducible. In contrast, ectopic expression of IKK alpha assembled into a complex with negligible I kappa B kinase activity. Moreover, IKK beta, but not IKK alpha, overexpression enhanced transcriptional activation of the CD28 response element in the IL-2 promoter. Conversely, only kinase-inactive IKK beta interfered in the activation of the IL-2 promoter. Sodium salicylate, an inhibitor of IKK beta, but not IKK alpha, activity, inhibited IL-2 promoter activation as well as IL-2 secretion and interfered in activation of both the heterodimeric as well as the homodimeric IKK complexes in primary CD4+ T cells. Taken together, these data demonstrate the presence of an IKK beta-mediated signaling pathway that is activated by TCR and CD28 coligation and regulates IL-2 promoter activity." @default.
• W2134246525 created "2016-06-24" @default.
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• W2134246525 date "1999-11-15" @default.
• W2134246525 modified "2023-09-23" @default.
• W2134246525 title "Primary human CD4+ T cells contain heterogeneous I kappa B kinase complexes: role in activation of the IL-2 promoter." @default.
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