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

Shona Moira McFarlane, G. Pashmi, Michelle Connell, Alison Littlejohn, Steven John Tucker, P. Vandenabeele, David Joseph MacEwan

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79 Citations (Scopus)

Abstract

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, electrophorefic 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. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.

Original languageEnglish
Pages (from-to)119-126
Number of pages7
JournalFEBS Letters
Volume515
Issue number1-3
DOIs
Publication statusPublished - 2002

Keywords

  • cytokine
  • receptor
  • subtype
  • signal transduction
  • kinase
  • tumour
  • CELL-DEATH
  • SIGNALING PATHWAY
  • KINASE
  • INDUCTION
  • DOMAIN
  • ALPHA
  • APOPTOSIS
  • IDENTIFICATION
  • PROLIFERATION
  • CYTOTOXICITY

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