The signaling adaptors and pathways activated by TNF superfamily

Members of the TNF receptor superfamily play pivotal roles in numerous biological events in metazoan organisms. Ligand-mediated trimerization by corresponding homo- or heterotrimeric ligands, the TNF family ligands, causes recruitment of several intracellular adaptors, which activate multiple signal...

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Bibliographic Details
Published in:Cytokine & growth factor reviews 2003-06, Vol.14 (3), p.193-209
Main Authors: Dempsey, Paul W, Doyle, Sean E, He, Jeannie Q, Cheng, Genhong
Format: Article
Language:English
Subjects:
Adaptor molecule
Animals
Apoptosis
Cell Survival
Humans
Inflammation - etiology
Ligands
Models, Biological
NF-kappa B - physiology
Proteins - chemistry
Proteins - physiology
Receptors, Tumor Necrosis Factor - physiology
Signal Transduction
TNF Receptor-Associated Factor 1
Tumor Necrosis Factor-alpha - physiology
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Summary:Members of the TNF receptor superfamily play pivotal roles in numerous biological events in metazoan organisms. Ligand-mediated trimerization by corresponding homo- or heterotrimeric ligands, the TNF family ligands, causes recruitment of several intracellular adaptors, which activate multiple signal transduction pathways. While recruitment of death domain (DD) containing adaptors such as Fas associated death domain (FADD) and TNFR associated DD (TRADD) can lead to the activation of a signal transduction pathway that induces apoptosis, recruitment of TRAF family proteins can lead to the activation of transcription factors such as, NF-κB and JNK thereby promoting cell survival and differentiation as well as immune and inflammatory responses. Individual TNF receptors are expressed in different cell types and have a range of affinities for various intracellular adaptors, which provide tremendous signaling and biological specificities. In addition, numerous signaling modulators are involved in regulating activities of signal transduction pathways downstream of receptors in this superfamily. Most of the TNF receptor superfamily members as well as many of their signaling mediators, have been uncovered in the last two decades. However, much remains unknown about how individual signal transduction pathways are regulated upon activation by any particular TNF receptor, under physiological conditions.
ISSN:1359-6101
DOI:10.1016/S1359-6101(03)00021-2