Article: article from journal or magazin.
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 of Biological Chemistry
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.
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
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