TNF receptor subtype signalling: Differences and cellular consequences

D. J. Macewan

Research output: Contribution to journalArticlepeer-review

499 Citations (Scopus)

Abstract

Tumour necrosis factor-alpha (TNFalpha) is a multifunctional cytokine belonging to a family of ligands with an associated family of receptor proteins. The pleiotropic actions of TNF range from proliferative responses such as cell growth and differentiation. to inflammatory effects and the mediation of immune responses. to destructive cellular outcomes such as apoptotic and necrotic cell death mechanisms. Activated TNF receptors mediate the association of distinct adaptor proteins that regulate a variety of signalling processes including kinase or phosphatase activation, lipase stimulation, and protease induction. Moreover, the cytokine regulates the activities of transcription factors, heterotrimeric or monomeric G-proteins and calcium ion homeostasis in order to orchestrate its cellular functions. This review addresses the structural basis of TNF signalling, the pathways employed with their cellular consequences, and focuses on the specific role played by each of the two TNF receptor isotypes, TNFRI and TNFR2. (C) 2002 Elsevier Science Inc. All rights reserved.
Original languageEnglish
Pages (from-to)477-492
Number of pages16
JournalCellular Signalling
Volume14
Issue number6
Publication statusPublished - 2002

Keywords

  • FACTOR-INDUCED APOPTOSIS
  • proliferation
  • apoptosis
  • signal transduction
  • kinase
  • lipase
  • receptor
  • SUPEROXIDE-DISMUTASE
  • inflammation
  • PHOSPHOLIPASE A(2)
  • protease
  • SMOOTH-MUSCLE-CELLS
  • HUMAN ENDOTHELIAL-CELLS
  • CYTOSOLIC
  • NF-KAPPA-B
  • ACTIVATED PROTEIN-KINASE
  • TYROSINE-PHOSPHATASE INHIBITORS
  • cytokine
  • TUMOR-NECROSIS-FACTOR
  • G-protein
  • phosphatase
  • necrosis
  • immune response
  • calcium homeostasis
  • ARACHIDONIC-ACID RELEASE
  • MANGANOUS

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