The human adaptor SARM negatively regulates adaptor protein TRIF–dependent Toll-like receptor signaling
Autor: | Andrew G. Bowie, Michael Carty, Martina Schröder, Rory Goodbody, Paul N. Moynagh, Julianne Stack |
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Jazyk: | angličtina |
Rok vydání: | 2006 |
Předmět: |
Transcriptional Activation
Chemokine Interferon Regulatory Factor-7 Immunology RNA interference Immunology and Allergy Humans RNA Small Interfering Receptor Cells Cultured Regulation of gene expression Armadillo Domain Proteins Gene knockdown Toll-like receptor biology Chemistry Toll-Like Receptors NF-kappa B Signal transducing adaptor protein biochemical phenomena metabolism and nutrition Cell biology Protein Structure Tertiary Toll-Like Receptor 3 Toll-Like Receptor 4 Adaptor Proteins Vesicular Transport Cytoskeletal Proteins Gene Expression Regulation TRIF Myeloid Differentiation Factor 88 Cancer research biology.protein Cytokines RNA Interference Chemokines Signal Transduction |
Popis: | Toll-like receptors discriminate between different pathogen-associated molecules and activate signaling cascades that lead to immune responses. The specificity of Toll-like receptor signaling occurs by means of adaptor proteins containing Toll-interleukin 1 receptor (TIR) domains. Activating functions have been assigned to four TIR adaptors: MyD88, Mal, TRIF and TRAM. Here we characterize a fifth TIR adaptor, SARM, as a negative regulator of TRIF-dependent Toll-like receptor signaling. Expression of SARM blocked gene induction 'downstream' of TRIF but not of MyD88. SARM associated with TRIF, and 'knockdown' of endogenous SARM expression by interfering RNA led to enhanced TRIF-dependent cytokine and chemokine induction. Thus, the fifth mammalian TIR adaptor SARM is a negative regulator of Toll-like receptor signaling. |
Databáze: | OpenAIRE |
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