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Tbk1  -  TANK-binding kinase 1

Mus musculus

Synonyms: 1200008B05Rik, AI462036, AW048562, Serine/threonine-protein kinase TBK1, T2K
 
 
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Disease relevance of Tbk1

 

High impact information on Tbk1

  • Together, these results demonstrate that TBK1 as well as, albeit to a lesser extent, IKK-i play a crucial role in the induction of IFN-beta and IFN-inducible genes in both TLR-stimulated and virus-infected EFs [2].
  • IRF-3 activation, in response not only to dsRNA but also to viral infection, was impaired in TBK1-deficient cells [2].
  • TBK1-deficient embryonic fibroblasts (EFs) showed dramatic decrease in induction of IFN-beta and IFN-inducible genes in response to LPS or dsRNA as well as after viral infection [2].
  • Thus, our studies suggest that TBK1 plays an important role in the Toll-like receptor-mediated IFN response and is redundant with IKK-i in the response of certain cell types to viral infection [1].
  • Here, we have compared the role and specificity of TBK1 in the type I IFN response to lipopolysaccharide (LPS), polyI:C, and viral challenge by examining IRF3 nuclear translocation, signal transducer and activator of transcription 1 phosphorylation, and induction of IFN-regulated genes [1].
 

Biological context of Tbk1

  • IFN-regulatory factor 3-dependent gene expression is defective in Tbk1-deficient mouse embryonic fibroblasts [3].
  • These results demonstrate that, like I-kappaB kinase beta and the RelA subunit of NF-kappaB, T2K is critical in protecting embryonic liver from apoptosis [4].
 

Anatomical context of Tbk1

  • The LPS and polyI:C-induced IFN responses were abolished and delayed, respectively, in macrophages from mice with a targeted disruption of the TBK1 gene [1].
  • Never theless, hematopoietic progenitors from T2K-deficient fetal liver support normal lymphocyte development [4].
 

Associations of Tbk1 with chemical compounds

References

  1. Differential requirement for TANK-binding kinase-1 in type I interferon responses to toll-like receptor activation and viral infection. Perry, A.K., Chow, E.K., Goodnough, J.B., Yeh, W.C., Cheng, G. J. Exp. Med. (2004) [Pubmed]
  2. The roles of two IkappaB kinase-related kinases in lipopolysaccharide and double stranded RNA signaling and viral infection. Hemmi, H., Takeuchi, O., Sato, S., Yamamoto, M., Kaisho, T., Sanjo, H., Kawai, T., Hoshino, K., Takeda, K., Akira, S. J. Exp. Med. (2004) [Pubmed]
  3. IFN-regulatory factor 3-dependent gene expression is defective in Tbk1-deficient mouse embryonic fibroblasts. McWhirter, S.M., Fitzgerald, K.A., Rosains, J., Rowe, D.C., Golenbock, D.T., Maniatis, T. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  4. Deficiency of T2K leads to apoptotic liver degeneration and impaired NF-kappaB-dependent gene transcription. Bonnard, M., Mirtsos, C., Suzuki, S., Graham, K., Huang, J., Ng, M., Itié, A., Wakeham, A., Shahinian, A., Henzel, W.J., Elia, A.J., Shillinglaw, W., Mak, T.W., Cao, Z., Yeh, W.C. EMBO J. (2000) [Pubmed]
  5. Specific inhibition of MyD88-independent signaling pathways of TLR3 and TLR4 by resveratrol: molecular targets are TBK1 and RIP1 in TRIF complex. Youn, H.S., Lee, J.Y., Fitzgerald, K.A., Young, H.A., Akira, S., Hwang, D.H. J. Immunol. (2005) [Pubmed]
 
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