NDLI: Toll-like receptor 3 associates with c-Src tyrosine kinase on endosomes to initiate antiviral signaling

Content Provider	PubMed Central
Author	Johnsen, Ingvild Bjellmo Nguyen, Thuy Thanh Ringdal, Monika Tryggestad, Anne Merete Bakke, Oddmund Lien, Egil Espevik, Terje Anthonsen, Marit W.
Copyright Year	2006
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.
Related Links	http://dx.doi.org/10.1038/sj.emboj.7601222
Ending Page	3346
Page Count	12
Starting Page	3335
File Format	PDF
ISSN	02614189
e-ISSN	14602075
Journal	The EMBO Journal
Issue Number	14
Volume Number	25
Language	English
Publisher Date	2006-07-26
Access Restriction	Open
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Immunology and Microbiology(all) Neuroscience(all) Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Microbiology Medicine Molecular Biology

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