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- Title
Novel roles of TLR3 tyrosine phosphorylation and PI3 kinase in double-stranded RNA signaling.
- Authors
Sarkar, Saumendra N; Peters, Kristi L; Elco, Christopher P; Sakamoto, Shuji; Pal, Srabani; Sen, Ganes C
- Abstract
Double-stranded RNA (dsRNA), a frequent byproduct of virus infection, is recognized by Toll-like receptor 3 (TLR3) to mediate innate immune response to virus infection. TLR3 signaling activates the transcription factor IRF-3 by its Ser/Thr phosphorylation, accompanied by its dimerization and nuclear translocation. It has been reported that the Ser/Thr kinase TBK-1 is essential for TLR3-mediated activation and phosphorylation of IRF-3. Here we report that dsRNA-activated phosphorylation of two specific tyrosine residues of TLR3 is essential for initiating two distinct signaling pathways. One involves activation of TBK-1 and the other recruits and activates PI3 kinase and the downstream kinase, Akt, leading to full phosphorylation and activation of IRF-3. When PI3 kinase is not recruited to TLR3 or its activity is blocked, IRF-3 is only partially phosphorylated and fails to bind the promoter of the target gene in dsRNA-treated cells. Thus, the PI3K-Akt pathway plays an essential role in TLR3-mediated gene induction.
- Publication
Nature structural & molecular biology, 2004, Vol 11, Issue 11, p1060
- ISSN
1545-9993
- Publication type
Journal Article
- DOI
10.1038/nsmb847