Bruton's tyrosine kinase phosphorylates Toll-like receptor 3 to initiate antiviral response

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 109; no. 15; pp. 5791 - 5796
• Main Authors: Lee, Koon-Guan, Xu, Shengli, Kang, Zi-Han, Huo, Jianxin, Huang, Mei, Liu, Dingxiang, Takeuchi, Osamu, Akira, Shizuo, Lam, Kong-Peng
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 10.04.2012; National Acad Sciences
• Subjects: Adaptor Proteins, Vesicular Transport - metabolism; Animals; Antibodies; Antiviral Agents - immunology; Antivirals; Binding sites; Biological Sciences; Cytokines; Cytokines - biosynthesis; Dengue virus; Dengue Virus - immunology; Dengue Virus - physiology; Double stranded RNA; Enzyme Activation; GTPase-Activating Proteins - metabolism; HEK293 Cells; Humans; Interferon-beta - biosynthesis; Macrophage Activation; Macrophages; Macrophages - enzymology; Macrophages - virology; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Mutation; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Protein-Serine-Threonine Kinases - metabolism; Protein-Tyrosine Kinases - deficiency; Protein-Tyrosine Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Receptors; Rodents; Signal transduction; T cell receptors; Toll like receptors; Toll-Like Receptor 3 - metabolism; Transcription factors; Transcription Factors - metabolism; Virus Replication

Toll-like receptor 3 (TLR3) mediates antiviral response by recognizing double-stranded RNA. Its cytoplasmic domain is tyrosine phosphorylated upon ligand binding and initiates downstream signaling via the adapter TIR-containing adaptor inducing interferon-β (TRIF). However, the kinase responsible fo...