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.