TRICK2, a new alternatively spliced receptor that transduces the cytotoxic signal from TRAIL

A subset of the tumour necrosis factor (TNF) receptor family contain a conserved intracellular motif, the death domain. Engagement of these receptors by their respective ligands initiates a signalling cascade that rapidly leads to cell death by apoptosis. We have cloned a new member of this family,...

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Bibliographic Details
Published in:Current biology 1997-09, Vol.7 (9), p.693-696
Main Authors: Screaton, Gavin R., Mongkolsapaya, Juthathip, Xu, Xiao-Ning, Cowper, Alison E., McMichael, Andrew J., Bell, John I.
Format: Article
Language:English
Subjects:
Alternative Splicing
Amino Acid Sequence
Animals
Apoptosis
Apoptosis Regulatory Proteins
Binding Sites
Cloning, Molecular
COS Cells
Membrane Glycoproteins - metabolism
Molecular Sequence Data
Receptors, TNF-Related Apoptosis-Inducing Ligand
Receptors, Tumor Necrosis Factor - genetics
Receptors, Tumor Necrosis Factor - metabolism
Signal Transduction
TNF-Related Apoptosis-Inducing Ligand
Tumor Necrosis Factor-alpha - metabolism
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Summary:A subset of the tumour necrosis factor (TNF) receptor family contain a conserved intracellular motif, the death domain. Engagement of these receptors by their respective ligands initiates a signalling cascade that rapidly leads to cell death by apoptosis. We have cloned a new member of this family, TRICK2, the TRAIL (TNF-related apoptosis-inducing ligand) receptor inducer of cell killing 2. TRICK2 is expressed in a number of cell types, and to particularly high levels in lymphocytes and spleen. Two isoforms of the TRICK2 mRNA are generated by alternative pre-mRNA splicing and differ by a 29 amino-acid extension to the extracellular domain. Overexpression of TRICK2 rapidly induced apoptosis in 293T cells; this induction was dependent upon the presence of the death domain of TRICK2. Using a soluble molecule containing the TRICK2 extracellular domain, we demonstrated that TRICK2, like DR4 [1], is a receptor for TRAIL/APO-2L [2,3] and could inhibit TRAIL-induced killing of lymphocyte lines, such as the Jurkat T-cell line. TRAIL is upregulated upon lymphocyte activation, as is the intensively studied ligand for Fas, FasL [4]. TRAIL and its receptors might therefore provide another system for the regulation of lymphocyte selection and proliferation, as well as providing an additional weapon in the armoury of cytotoxic lymphocytes.
ISSN:0960-9822
1879-0445
DOI:10.1016/S0960-9822(06)00297-1