The tumor necrosis factor-related apoptosis-inducing ligand receptors TRAIL-R1 and TRAIL-R2 have distinct cross-linking requirements for initiation of apoptosis and are non-redundant in JNK activation.

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Serval ID
serval:BIB_3ED2A05AC91F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The tumor necrosis factor-related apoptosis-inducing ligand receptors TRAIL-R1 and TRAIL-R2 have distinct cross-linking requirements for initiation of apoptosis and are non-redundant in JNK activation.
Journal
Journal of Biological Chemistry
Author(s)
Mühlenbeck F., Schneider P., Bodmer J.L., Schwenzer R., Hauser A., Schubert G., Scheurich P., Moosmayer D., Tschopp J., Wajant H.
ISSN
0021-9258 (Print)
ISSN-L
0021-9258
Publication state
Published
Issued date
2000
Volume
275
Number
41
Pages
32208-32213
Language
english
Abstract
Overexpression of the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptors, TRAIL-R1 and TRAIL-R2, induces apoptosis and activation of NF-kappaB in cultured cells. In this study, we have demonstrated differential signaling capacities by both receptors using either epitope-tagged soluble TRAIL (sTRAIL) or sTRAIL that was cross-linked with a monoclonal antibody. Interestingly, sTRAIL was sufficient for induction of apoptosis only in cell lines that were killed by agonistic TRAIL-R1- and TRAIL-R2-specific IgG preparations. Moreover, in these cell lines interleukin-6 secretion and NF-kappaB activation were induced by cross-linked or non-cross-linked anti-TRAIL, as well as by both receptor-specific IgGs. However, cross-linking of sTRAIL was required for induction of apoptosis in cell lines that only responded to the agonistic anti-TRAIL-R2-IgG. Interestingly, activation of c-Jun N-terminal kinase (JNK) was only observed in response to either cross-linked sTRAIL or anti-TRAIL-R2-IgG even in cell lines where both receptors were capable of signaling apoptosis and NF-kappaB activation. Taken together, our data suggest that TRAIL-R1 responds to either cross-linked or non-cross-linked sTRAIL which signals NF-kappaB activation and apoptosis, whereas TRAIL-R2 signals NF-kappaB activation, apoptosis, and JNK activation only in response to cross-linked TRAIL.
Keywords
Antibodies, Monoclonal/immunology, Apoptosis, Apoptosis Regulatory Proteins, Enzyme Activation, Flow Cytometry, Humans, Immunoglobulin G/immunology, Interleukin-6/metabolism, JNK Mitogen-Activated Protein Kinases, Membrane Glycoproteins/agonists, Membrane Glycoproteins/immunology, Mitogen-Activated Protein Kinases/metabolism, NF-kappa B/metabolism, Receptor Aggregation, Receptors, TNF-Related Apoptosis-Inducing Ligand, Receptors, Tumor Necrosis Factor/agonists, Receptors, Tumor Necrosis Factor/metabolism, Signal Transduction, Staphylococcal Protein A/immunology, TNF-Related Apoptosis-Inducing Ligand, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha/agonists, Tumor Necrosis Factor-alpha/immunology
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 15:19
Last modification date
18/01/2020 7:08
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