Differential activation of nuclear factor‐κB by tumour necrosis factor receptor subtypes. TNFR1 predominates whereas TNFR2 activates transcription poorly

FEBS Letters

MacEwan, David J²  Pashmi, Ghazaleh²  Vandenabeele, Peter¹  Tucker, Steven J²  Connell, Michelle C²  McFarlane, Shona M²  Littlejohn, Alison F² 

[1]Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology, University of Gent, Ledeganckstraat 35, B-9000 Gent, Belgium

[2]Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK

关键词: Cytokine;    Receptor;    Subtype;    Signal transduction;    Kinase;    Tumour;    AEBSF;    4-(2-aminoethyl)benzene sulfonyl fluoride;    EMSA;    electrophoretic mobility shift assay;    (e)GFP;    (enhanced) green fluorescent protein;    hrGFP;    humanised renilla green fluorescent protein;    NF-κB;    nuclear factor κB;    IκB;    inhibitor of NF-κB;    IKK;    IκB kinase;    JNK;    c-Jun N-terminal kinase;    NIK;    NF-κB-inducing kinase;    RIP;    receptor-interacting protein;    TNF;    tumour necrosis factor-α;    TNFR;    TNF receptor;    TNFR1;    type I 55 kDa TNFR;    TNFR2;    type II 75 kDa TNFR;    TRAF;    TNFR-associating factor;   

DOI  :  10.1016/S0014-5793(02)02450-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Tumour necrosis factor-α (TNF-α) signals though two receptors, TNFR1 and TNFR2. TNFR1 has a role in cytotoxicity, whereas TNFR2 regulates death responses or proliferation. TNF activates pro-inflammatory transcription factor nuclear factor-κB (NF-κB) by uncertain signalling mechanisms. Here we report the contribution of each TNFR towards the NF-κB activation processes. In human cells expressing endogenous or exogenous TNFR2, in addition to TNFR1, we found both TNFRs capable of activating NF-κB, as measured by IκBα (inhibitor of NF-κB) degradation, electrophoretic mobility shift assay and NF-κB gene reporter assays. TNFR2 activation did not degrade IκBβ. However, TNF-effects on NF-κB activation occurred predominantly through TNFR1, with TNFR2 activating the transcription factor poorly.

【 授权许可】

Unknown