Tumor necrosis factor-α signals to the IFN-γ receptor complex to increase Stat1α activation

被引:17
作者
Han, YL
Rogers, N
Ransohoff, RM
机构
[1] Cleveland Clin Fdn, Lerner Res Inst, Dept Neurosci, Cleveland, OH 44195 USA
[2] Imperial Canc Res Fund Labs, London, England
[3] Cleveland Clin Fdn, Dept Neurol, Mellen Ctr Multiple Sclerosis Treatment & Res, Cleveland, OH 44195 USA
关键词
D O I
10.1089/107999099313578
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We describe a novel mechanism of signaling interaction through which tumor necrosis factor-alpha (TNF-alpha) treatment augments interferon-gamma (IFN-gamma)-induced Stat1 alpha DNA-binding complexes and transcriptional activation of a Stat-binding element. In TNF-alpha-treated cells, IFN-gamma-induced phosphorylation of Jak2 kinase is increased, Jak2 kinase activity is enhanced, and genetic studies indicate that TNF-alpha requires Jak2 kinase activity to enhance Stat1 alpha tyrosine phosphorylation, Increased Jak2 and Stat1 alpha phosphorylation are observed within minutes of coexposure to TNF-alpha/IFN-gamma, suggesting a direct signaling interaction. IFN-gamma receptor chain 1 (IFNGR-1) tyrosine phosphorylation is markedly enhanced in cells treated with TNF-alpha/IFN-gamma without alteration in receptor levels. Thus, there exists a direct signaling interaction between TNF-alpha and IFN-gamma, independent of cooperating enhancer elements, that may be relevant for cytokine action during immune-mediated host defense and inflammatory processes.
引用
收藏
页码:731 / 740
页数:10
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