Differential activation of nuclear factor-kappaB by tumour necrosis factor receptor subtypes. TNFR1 predominates whereas TNFR2 activates transcription poorly.
Tumour necrosis factor-alpha (TNF-alpha) 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-kappaB (NF-kappaB) by uncertain signalling mechanisms. Here we report the contribution of each TNFR towards the NF-kappaB activation processes. In human cells expressing endogenous or exogenous TNFR2, in addition to TNFR1, we found both TNFRs capable of activating NF-kappaB, as measured by IkappaBalpha (inhibitor of NF-kappaB) degradation, electrophoretic mobility shift assay and NF-kappaB gene reporter assays. TNFR2 activation did not degrade IkappaBbeta. However, TNF-effects on NF-kappaB activation occurred predominantly through TNFR1, with TNFR2 activating the transcription factor poorly.
McFarlane
Shona M
SM
Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, AB25 2ZD, Aberdeen, UK.
Pashmi
Ghazaleh
G
Connell
Michelle C
MC
Littlejohn
Alison F
AF
Tucker
Steven J
SJ
Vandenabeele
Peter
P
MacEwan
David J
DJ
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D020672:I-kappa B Proteins; D007106:Immune Sera / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*; D014162:Transfection
D015703:Antigens, CD; D004268:DNA-Binding Proteins; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D007106:Immune Sera; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011993:Recombinant Fusion Proteins; D000072000:NF-KappaB Inhibitor alpha; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases