TNF receptor subtype signalling: differences and cellular consequences

David Joseph MacEwan

    Research output: Contribution to journalArticle

    485 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 pages15
    JournalCellular Signalling
    Volume14
    Issue number6
    DOIs
    Publication statusPublished - 2002

    Keywords

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

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