Three is better than one: pre-ligand receptor assembly in the regulation of TNF receptor signaling.

Citation data:

Cytokine, ISSN: 1043-4666, Vol: 37, Issue: 2, Page: 101-7

Publication Year:
2007
Usage 95
Abstract Views 87
Link-outs 8
Captures 92
Readers 88
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Citations 108
Citation Indexes 108
Repository URL:
https://escholarship.umassmed.edu/oapubs/1250
PMID:
17449269
DOI:
10.1016/j.cyto.2007.03.005
PMCID:
PMC1965282
Author(s):
Chan, Francis Ka-Ming
Publisher(s):
Elsevier BV
Tags:
Medicine; Immunology and Microbiology; Biochemistry, Genetics and Molecular Biology; Animals; Antigens, CD95; Humans; Ligands; Protein Structure, Quaternary; Receptors, TNF-Related Apoptosis-Inducing Ligand; Receptors, Tumor Necrosis Factor; Signal Transduction; T-Lymphocytes; Life Sciences; Medicine and Health Sciences
review description
The tumor necrosis factor (TNF) family of cytokines and their receptors regulates many areas of metazoan biology. Specifically, this cytokine-receptor family plays crucial roles in regulating myriad aspects of immune development and functions. Disruption of ligand-receptor interaction or downstream signal transduction components in the TNF family often leads to pathological conditions. Historically, members of the TNF receptor family (TNFRs) were thought to exist as monomeric receptor chains prior to stimulation. Binding of the trimeric ligand then induces the trimerization of the receptors and activation of downstream signaling. However, recent evidence indicates that many TNFRs exist as pre-assembled oligomers on the cell surface. Pre-ligand assembly of TNFR oligomers is mediated by the pre-ligand assembly domain (PLAD), which resides within the membrane distal cysteine-rich domain of the receptors. Growing evidence indicates that PLAD-mediated receptor association regulates cellular responses to TNF-like cytokines, especially in cells of the immune system. Thus, targeting pre-ligand assembly may offer new possibilities for therapeutic intervention in different pathological conditions involving TNF-like cytokines.