Glucocorticoid-Induced TNF Receptor, a Costimulatory Receptor on Naive and Activated T Cells, Uses TNF Receptor-Associated Factor 2 in a Novel Fashion as an Inhibitor of NF-κB Activation
| Autor: | Robert H. Arch, Edward M. Esparza |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Cytoplasm
TRAF2 Molecular Sequence Data Immunology Down-Regulation Mice Transgenic Receptors Nerve Growth Factor Biology Lymphocyte Activation Transfection Resting Phase Cell Cycle Receptors Tumor Necrosis Factor Cell Line Mice Glucocorticoid-Induced TNFR-Related Protein Immune system Animals Humans Immunology and Allergy Amino Acid Sequence Receptor Conserved Sequence Tumor Necrosis Factor alpha-Induced Protein 3 Intracellular Signaling Peptides and Proteins NF-kappa B Nuclear Proteins Proteins Signal transducing adaptor protein Hydrogen-Ion Concentration TNF Receptor-Associated Factor 2 Protein Structure Tertiary Cell biology DNA-Binding Proteins Cysteine Endopeptidases Protein Transport TNF receptor associated factor Tumor Necrosis Factors Signal transduction Carrier Proteins |
| Zdroj: | The Journal of Immunology. 174:7875-7882 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.174.12.7875 |
| Popis: | Glucocorticoid-induced TNFR (GITR) has been implicated as an essential regulator of immune responses to self tissues and pathogens. We have recently shown that GITR-induced cellular events promote survival of naive T cells, but are insufficient to protect against activation-induced cell death. However, the molecular mechanisms of GITR-induced signal transduction that influence physiologic and pathologic immune responses are not well understood. TNFR-associated factors (TRAFs) are pivotal adapter proteins involved in signal transduction pathways of TNFR-related proteins. Yeast two-hybrid assays and studies in HEK293 cells and primary lymphocytes indicated interactions between TRAF2 and GITR mediated by acidic residues in the cytoplasmic domain of the receptor. GITR-induced activation of NF-κB is blocked by A20, an NF-κB-inducible protein that interacts with TRAFs and functions in a negative feedback mechanism downstream of other TNFRs. Interestingly, in contrast with its effects on signaling triggered by other TNFRs, our functional studies revealed that TRAF2 plays a novel inhibitory role in GITR-triggered NF-κB activation. |
| Databáze: | OpenAIRE |
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