ridm@nrct.go.th   ระบบคลังข้อมูลงานวิจัยไทย   รายการโปรดที่คุณเลือกไว้

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

หน่วยงาน Nanyang Technological University, Singapore

รายละเอียด

ชื่อเรื่อง : Bruton's tyrosine kinase phosphorylates Toll-like receptor 3 to initiate antiviral response
นักวิจัย : Lee, K.-G. , Xu, S. , Kang, Z.-H. , Huo, J. , Huang, M. , Liu, D. , Takeuchi, O. , Akira, Shizuo , Lam, K.-P.
คำค้น : DRNTU::Science::Biological sciences
หน่วยงาน : Nanyang Technological University, Singapore
ผู้ร่วมงาน : -
ปีพิมพ์ : 2555
อ้างอิง : Lee, K. G., Xu, S., Kang, Z. H., Huo, J., Huang, M., Liu, D., et al. (2012). Bruton's tyrosine kinase phosphorylates Toll-like receptor 3 to initiate antiviral response. Proceedings of the national academy of sciences, 109(15), 5791-5796. , http://hdl.handle.net/10220/12357 , http://dx.doi.org/10.1073/pnas.1119238109
ที่มา : -
ความเชี่ยวชาญ : -
ความสัมพันธ์ : Proceedings of the national academy of sciences
ขอบเขตของเนื้อหา : -
บทคัดย่อ/คำอธิบาย :

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 for TLR3 phosphorylation remains unknown. We show here that Bruton's tyrosine kinase (BTK)-deficient macrophages failed to secrete inflammatory cytokines and IFN-β upon TLR3 stimulation and were impaired in clearing intracellular dengue virus infection. Mutant mice were also less susceptible to D-galactosamine/p(I:C)-induced sepsis. In the absence of BTK, TLR3-induced phosphoinositide 3-kinase (PI3K), AKT and MAPK signaling and activation of NFκB, IRF3, and AP-1 transcription factors were all defective. We demonstrate that BTK directly phosphorylates TLR3 and in particular the critical Tyr759 residue. BTK point mutations that abrogate or led to constitutive kinase activity have opposite effects on TLR3 phosphorylation. Loss of BTK also compromises the formation of the downstream TRIF/receptor-interacting protein 1 (RIP1)/TBK1 complex. Thus, BTK plays a critical role in initiating TLR3 signaling.

บรรณานุกรม :
Lee, K.-G. , Xu, S. , Kang, Z.-H. , Huo, J. , Huang, M. , Liu, D. , Takeuchi, O. , Akira, Shizuo , Lam, K.-P. . (2555). Bruton's tyrosine kinase phosphorylates Toll-like receptor 3 to initiate antiviral response.
    กรุงเทพมหานคร : Nanyang Technological University, Singapore.
Lee, K.-G. , Xu, S. , Kang, Z.-H. , Huo, J. , Huang, M. , Liu, D. , Takeuchi, O. , Akira, Shizuo , Lam, K.-P. . 2555. "Bruton's tyrosine kinase phosphorylates Toll-like receptor 3 to initiate antiviral response".
    กรุงเทพมหานคร : Nanyang Technological University, Singapore.
Lee, K.-G. , Xu, S. , Kang, Z.-H. , Huo, J. , Huang, M. , Liu, D. , Takeuchi, O. , Akira, Shizuo , Lam, K.-P. . "Bruton's tyrosine kinase phosphorylates Toll-like receptor 3 to initiate antiviral response."
    กรุงเทพมหานคร : Nanyang Technological University, Singapore, 2555. Print.
Lee, K.-G. , Xu, S. , Kang, Z.-H. , Huo, J. , Huang, M. , Liu, D. , Takeuchi, O. , Akira, Shizuo , Lam, K.-P. . Bruton's tyrosine kinase phosphorylates Toll-like receptor 3 to initiate antiviral response. กรุงเทพมหานคร : Nanyang Technological University, Singapore; 2555.