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- Title
Toll-like receptor 3 associates with c-Src tyrosine kinase on endosomes to initiate antiviral signaling.
- Authors
Johnsen, Ingvild Bjellmo; Nguyen, Thuy Thanh; Ringdal, Monika; Tryggestad, Anne Merete; Bakke, Oddmund; Lien, Egil; Espevik, Terje; Anthonsen, Marit W
- Abstract
Double-stranded RNA (dsRNA) is produced during the replication cycle of most viruses and triggers antiviral immune responses through Toll-like receptor 3 (TLR3). However, the molecular mechanisms and subcellular compartments associated with dsRNA-TLR3-mediated signaling are largely unknown. Here we show that c-Src tyrosine kinase is activated by dsRNA in human monocyte-derived dendritic cells, and is recruited to TLR3 in a dsRNA-dependent manner. DsRNA-induced activation of interferon-regulatory factor 3 and signal transducer and activator of transcription 1 was abolished in Src kinase-deficient cells, and restored by adding back c-Src, suggesting a central role of c-Src in antiviral immunity. We also provide evidence that TLR3 is localized in the endoplasmic reticulum of unstimulated cells, moves to dsRNA-containing endosomes in response to dsRNA, and colocalizes with c-Src on endosomes containing dsRNA in the lumen. These results provide novel insight into the molecular mechanisms of TLR3-mediated signaling, which may contribute to the understanding of innate immune responses during viral infections.
- Publication
The EMBO journal, 2006, Vol 25, Issue 14, p3335
- ISSN
0261-4189
- Publication type
Journal Article
- DOI
10.1038/sj.emboj.7601222