Gene Symbol: Tbk1
Description: TANK-binding kinase 1
Alias: 1200008B05Rik, AI462036, AW048562, serine/threonine-protein kinase TBK1, T2K
Species: mouse
Products:     Tbk1

Top Publications

  1. Soulat D, Burckstummer T, Westermayer S, Goncalves A, Bauch A, Stefanovic A, et al. The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response. EMBO J. 2008;27:2135-46 pubmed publisher
    TANK-binding kinase 1 (TBK1) is of central importance for the induction of type-I interferon (IFN) in response to pathogens. We identified the DEAD-box helicase DDX3X as an interaction partner of TBK1...
  2. Unterholzner L, Keating S, Baran M, Horan K, Jensen S, Sharma S, et al. IFI16 is an innate immune sensor for intracellular DNA. Nat Immunol. 2010;11:997-1004 pubmed publisher
    ..IFI16 (p204) is the first PYHIN protein to our knowledge shown to be involved in IFN-? induction. Thus, the PYHIN proteins IFI16 and AIM2 form a new family of innate DNA sensors we call 'AIM2-like receptors' (ALRs). ..
  3. Joung S, Park Z, Rani S, Takeuchi O, Akira S, Lee J. Akt contributes to activation of the TRIF-dependent signaling pathways of TLRs by interacting with TANK-binding kinase 1. J Immunol. 2011;186:499-507 pubmed publisher
    ..We show that Akt is a downstream molecule of TRIF/TANK-binding kinase 1 (TBK1) and plays an important role in the activation of IRF3 by TLR3 and -4 agonists...
  4. O Connell R, Vaidya S, Perry A, Saha S, Dempsey P, Cheng G. Immune activation of type I IFNs by Listeria monocytogenes occurs independently of TLR4, TLR2, and receptor interacting protein 2 but involves TNFR-associated NF kappa B kinase-binding kinase 1. J Immunol. 2005;174:1602-7 pubmed
    ..pathway involving the serine-threonine kinase TNFR-associated NF-kappaB kinase (TANK)-binding kinase 1 (TBK1)...
  5. Gleason C, Ordureau A, Gourlay R, Arthur J, Cohen P. Polyubiquitin binding to optineurin is required for optimal activation of TANK-binding kinase 1 and production of interferon ?. J Biol Chem. 2011;286:35663-74 pubmed publisher
    TANK-binding kinase (TBK1) is essential for transcription of the interferon (IFN) ? gene in response to lipopolysaccharide (LPS) and double-stranded RNA, but the molecular mechanisms that underlie the activation of TBK1 are incompletely ..
  6. Ishii K, Kawagoe T, Koyama S, Matsui K, Kumar H, Kawai T, et al. TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines. Nature. 2008;451:725-9 pubmed publisher
    ..Here we demonstrate in vivo that TANK-binding kinase 1 (TBK1), a non-canonical IkappaB kinase, mediates the adjuvant effect of DNA vaccines and is essential for its ..
  7. Shu C, Yi G, Watts T, Kao C, Li P. Structure of STING bound to cyclic di-GMP reveals the mechanism of cyclic dinucleotide recognition by the immune system. Nat Struct Mol Biol. 2012;19:722-4 pubmed publisher
    ..Guanines of c-di-GMP stack against the phenolic rings of a conserved tyrosine, and mutations at the c-di-GMP binding surface reduce nucleotide binding and affect signaling. ..
  8. Ma Y, Jin H, Valyi Nagy T, Cao Y, Yan Z, He B. Inhibition of TANK binding kinase 1 by herpes simplex virus 1 facilitates productive infection. J Virol. 2012;86:2188-96 pubmed publisher
    ..Here we report that ?(1)34.5 inhibits TANK binding kinase 1 (TBK1) through its amino-terminal sequences, which facilitates viral replication and neuroinvasion...
  9. Matsui K, Kumagai Y, Kato H, Sato S, Kawagoe T, Uematsu S, et al. Cutting edge: Role of TANK-binding kinase 1 and inducible IkappaB kinase in IFN responses against viruses in innate immune cells. J Immunol. 2006;177:5785-9 pubmed
    TANK-binding kinase 1 (TBK1) and inducible IkappaB kinase (IKK-i) are involved in the activation of transcription factors inducing the production of type I IFNs...

More Information


  1. Ishii K, Coban C, Kato H, Takahashi K, Torii Y, Takeshita F, et al. A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA. Nat Immunol. 2006;7:40-8 pubmed
    ..IRF3 and the promoter of the gene encoding interferon-beta through a signaling pathway that required the kinases TBK1 and IKKi, whereas there was substantial activation of transcription factor NF-kappaB independent of both TBK and ..
  2. Kato H, Sato S, Yoneyama M, Yamamoto M, Uematsu S, Matsui K, et al. Cell type-specific involvement of RIG-I in antiviral response. Immunity. 2005;23:19-28 pubmed
    ..In contrast, plasmacytoid DCs, which produce large amounts of IFN-alpha, use the TLR system rather than RIG-I for viral detection. Taken together, RIG-I and the TLR system exert antiviral responses in a cell type-specific manner...
  3. Hemmi H, Takeuchi O, Sato S, Yamamoto M, Kaisho T, Sanjo H, et al. The roles of two IkappaB kinase-related kinases in lipopolysaccharide and double stranded RNA signaling and viral infection. J Exp Med. 2004;199:1641-50 pubmed
    ..Recently, two IkappaB kinase (IKK)-related kinases, inducible IkappaB kinase (IKK-i) and TANK-binding kinase 1 (TBK1), were suggested to act as IRF-3 kinases and be involved in IFN-beta production in Toll-like receptor (TLR) ..
  4. Parvatiyar K, Barber G, Harhaj E. TAX1BP1 and A20 inhibit antiviral signaling by targeting TBK1-IKKi kinases. J Biol Chem. 2010;285:14999-5009 pubmed publisher
    ..Activation of IRF3 requires C-terminal phosphorylation by the upstream kinases TBK1-IKKi, where IRF3 phosphorylation promotes dimerization, and subsequent nuclear translocation to the IFNbeta ..
  5. Jin J, Xiao Y, Chang J, Yu J, Hu H, Starr R, et al. The kinase TBK1 controls IgA class switching by negatively regulating noncanonical NF-?B signaling. Nat Immunol. 2012;13:1101-9 pubmed publisher
    ..Here we identify the kinase TBK1 as a pivotal negative regulator of class switching to the immunoglobulin A (IgA) isotype...
  6. Pomerantz J, Baltimore D. NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase. EMBO J. 1999;18:6694-704 pubmed
    ..In this report, we investigate the mechanism of the stimulatory activity of TANK. We find that TANK interacts with TBK1 (TANK-binding kinase 1), a novel IKK-related kinase that can activate NF-kappaB in a kinase-dependent manner...
  7. Radtke A, Delbridge L, Balachandran S, Barber G, O Riordan M. TBK1 protects vacuolar integrity during intracellular bacterial infection. PLoS Pathog. 2007;3:e29 pubmed
    TANK-binding kinase-1 (TBK1) is an integral component of Type I interferon induction by microbial infection...
  8. Wild P, Farhan H, McEwan D, Wagner S, Rogov V, Brady N, et al. Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth. Science. 2011;333:228-33 pubmed publisher
    ..The protein kinase TANK binding kinase 1 (TBK1) phosphorylated optineurin on serine-177, enhancing LC3 binding affinity and autophagic clearance of cytosolic ..
  9. Zhang M, Wu X, Lee A, Jin W, Chang M, Wright A, et al. Regulation of IkappaB kinase-related kinases and antiviral responses by tumor suppressor CYLD. J Biol Chem. 2008;283:18621-6 pubmed publisher
    The IkappaB kinase (IKK)-related kinases, IKKepsilon and TBK1, participate in the induction of type I interferons (IFNs) during viral infections...
  10. Wang L, Li S, Dorf M. NEMO binds ubiquitinated TANK-binding kinase 1 (TBK1) to regulate innate immune responses to RNA viruses. PLoS ONE. 2012;7:e43756 pubmed publisher
    ..b>TBK1 is a critical kinase implicated in RLR-dependent IFN transcription...
  11. Ou Y, Torres M, Ram R, Formstecher E, Roland C, Cheng T, et al. TBK1 directly engages Akt/PKB survival signaling to support oncogenic transformation. Mol Cell. 2011;41:458-70 pubmed publisher
    The innate immune-signaling kinase, TBK1, couples pathogen surveillance to induction of host defense mechanisms. Pathological activation of TBK1 in cancer can overcome programmed cell death cues, enabling cells to survive oncogenic stress...
  12. Xie X, Zhang D, Zhao B, Lu M, You M, Condorelli G, et al. IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by direct phosphorylation. Proc Natl Acad Sci U S A. 2011;108:6474-9 pubmed publisher
    ..Here we show that the atypical I?B kinase ? and TANK-binding kinase 1 (IKK?/TBK1) phosphorylate AKT on both the hydrophobic motif and the activation loop in a manner dependent on PI3K signaling...
  13. Bonnard M, Mirtsos C, Suzuki S, Graham K, Huang J, Ng M, et al. Deficiency of T2K leads to apoptotic liver degeneration and impaired NF-kappaB-dependent gene transcription. EMBO J. 2000;19:4976-85 pubmed
    ..In this study, we purified and characterized a novel kinase (T2K, also known as TBK1 or NAK), which associates with TRAF2 and exhibits kinase activity towards I-kappaBalpha in vitro...
  14. Guo B, Cheng G. Modulation of the interferon antiviral response by the TBK1/IKKi adaptor protein TANK. J Biol Chem. 2007;282:11817-26 pubmed
    ..Thus, TANK may be a critical adaptor that regulates the assembly of the TANK-binding kinase 1-inducible IkappaB kinase complex with upstream signaling molecules in multiple antiviral pathways. ..
  15. Perry A, Chow E, Goodnough J, Yeh W, Cheng G. Differential requirement for TANK-binding kinase-1 in type I interferon responses to toll-like receptor activation and viral infection. J Exp Med. 2004;199:1651-8 pubmed
    TANK-binding kinase-1 (TBK1) and the inducible IkappaB kinase (IKK-i) have been shown recently to activate interferon (IFN) regulatory factor-3 (IRF3), the primary transcription factor regulating induction of type I IFNs...
  16. McWhirter S, Fitzgerald K, Rosains J, Rowe D, Golenbock D, Maniatis T. IFN-regulatory factor 3-dependent gene expression is defective in Tbk1-deficient mouse embryonic fibroblasts. Proc Natl Acad Sci U S A. 2004;101:233-8 pubmed
    ..IKK)-related kinases, IKK-epsilon and Traf family member-associated NF-kappaB activator (TANK)-binding kinase 1 (TBK1), in the phosphorylation of IRF3...
  17. Oshiumi H, Miyashita M, Matsumoto M, Seya T. A distinct role of Riplet-mediated K63-Linked polyubiquitination of the RIG-I repressor domain in human antiviral innate immune responses. PLoS Pathog. 2013;9:e1003533 pubmed publisher
    ..autorepression of its N-terminal CARDs, which leads to the association of RIG-I with TRIM25 ubiquitin ligase and TBK1 protein kinase. Our data indicate that Riplet is a prerequisite for TRIM25 to activate RIG-I signaling...
  18. Miyahira A, Shahangian A, Hwang S, Sun R, Cheng G. TANK-binding kinase-1 plays an important role during in vitro and in vivo type I IFN responses to DNA virus infections. J Immunol. 2009;182:2248-57 pubmed publisher
    TANK-binding kinase-1 (TBK1) and the inducible IkappaB kinase (IKK-i) have recently been shown to activate type I IFN responses elicited by intracellular detection of RNA or DNA from infecting viruses...
  19. Wang C, Chen T, Zhang J, Yang M, Li N, Xu X, et al. The E3 ubiquitin ligase Nrdp1 'preferentially' promotes TLR-mediated production of type I interferon. Nat Immunol. 2009;10:744-52 pubmed publisher
    ..MyD88-dependent activation of transcription factors NF-kappaB and AP-1 while promoting activation of the kinase TBK1 and transcription factor IRF3...
  20. Chien Y, Kim S, Bumeister R, Loo Y, Kwon S, Johnson C, et al. RalB GTPase-mediated activation of the IkappaB family kinase TBK1 couples innate immune signaling to tumor cell survival. Cell. 2006;127:157-70 pubmed
    ..find that the RalB/Sec5 effector complex directly recruits and activates the atypical IkappaB kinase family member TBK1. In cancer cells, constitutive engagement of this pathway, via chronic RalB activation, restricts initiation of ..
  21. Ikeda F, Hecker C, Rozenknop A, Nordmeier R, Rogov V, Hofmann K, et al. Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes. EMBO J. 2007;26:3451-62 pubmed
    TANK-binding kinase 1 (TBK1/NAK/T2K) and I-kappaB Kinase (IKK-i/IKK-epsilon) play important roles in the regulation of interferon (IFN)-inducible genes during the immune response to bacterial and viral infections...
  22. Zhao T, Yang L, Sun Q, Arguello M, Ballard D, Hiscott J, et al. The NEMO adaptor bridges the nuclear factor-kappaB and interferon regulatory factor signaling pathways. Nat Immunol. 2007;8:592-600 pubmed
    ..activation of IRF3 and IRF7 depended on the NF-kappaB modulator NEMO, which acted 'upstream' of the kinases TBK1 and IKKepsilon...
  23. Goncalves A, Burckstummer T, Dixit E, Scheicher R, Górna M, Karayel E, et al. Functional dissection of the TBK1 molecular network. PLoS ONE. 2011;6:e23971 pubmed publisher
    TANK-binding kinase 1 (TBK1) and inducible I?B-kinase (IKK-i) are central regulators of type-I interferon induction...
  24. Qu F, Gao H, Zhu S, Shi P, Zhang Y, Liu Y, et al. TRAF6-dependent Act1 phosphorylation by the I?B kinase-related kinases suppresses interleukin-17-induced NF-?B activation. Mol Cell Biol. 2012;32:3925-37 pubmed publisher
    ..Here we show that TANK binding kinase 1 (TBK1), the other IKK-related kinase, directly phosphorylated Act1 on three other Ser sites to suppress IL-17R-mediated ..
  25. Liu T, Yang Q, Li M, Zhong B, Ran Y, Liu L, et al. LSm14A Plays a Critical Role in Antiviral Immune Responses by Regulating MITA Level in a Cell-Specific Manner. J Immunol. 2016;196:5101-11 pubmed publisher
    ..Our findings reveal a nuclear mRNA precursor processing and cell-specific regulatory mechanism of antiviral immune responses. ..
  26. Cai B, Wu J, Yu X, Su X, Wang R. FOSL1 Inhibits Type I Interferon Responses to Malaria and Viral Infections by Blocking TBK1 and TRAF3/TRIF Interactions. MBio. 2017;8: pubmed publisher
    ..factor 3 (TRAF3), TIR domain-containing adapter inducing IFN-? (TRIF), and Tank-binding kinase 1 (TBK1) via impairing K63-linked polyubiquitination of TRAF3 and TRIF...
  27. Ge M, Luo Z, Qiao Z, Zhou Y, Cheng X, Geng Q, et al. HERP Binds TBK1 To Activate Innate Immunity and Repress Virus Replication in Response to Endoplasmic Reticulum Stress. J Immunol. 2017;199:3280-3292 pubmed publisher
  28. Panda S, Nilsson J, Gekara N. Deubiquitinase MYSM1 Regulates Innate Immunity through Inactivation of TRAF3 and TRAF6 Complexes. Immunity. 2015;43:647-59 pubmed publisher
    ..This study identifies MYSM1 as a key negative regulator of the innate immune system that guards against an overzealous self-destructive immune response. ..
  29. Li Z, Liu G, Sun L, Teng Y, Guo X, Jia J, et al. PPM1A regulates antiviral signaling by antagonizing TBK1-mediated STING phosphorylation and aggregation. PLoS Pathog. 2015;11:e1004783 pubmed publisher
    ..its phosphatase activity-dependent manner, and in a line with this, PPM1A catalytically dephosphorylates STING and TBK1 in vitro...
  30. Li L, Zhao Y, Zhang H. P16INK4a upregulation mediated by TBK1 induces retinal ganglion cell senescence in ischemic injury. Cell Death Dis. 2017;8:e2752 pubmed publisher
    ..Here, we demonstrate that TANK-binding protein 1 (TBK1) is upregulated in acute IOP elevation-induced ischemic retinas mouse model...
  31. Lee S, Jhun J, Byun J, Kim E, Jung K, Lee J, et al. IL-17 axis accelerates the inflammatory progression of obese in mice via TBK1 and IKBKE pathway. Immunol Lett. 2017;184:67-75 pubmed publisher
    ..Adipgenesis can be regulated by IL-17 and it causes TBK1 activation. The inhibition of TBK1 and the inhibition of I IKBKE reduces inflammatory response and improves obesity...
  32. Xiao Y, Zou Q, Xie X, Liu T, Li H, Jie Z, et al. The kinase TBK1 functions in dendritic cells to regulate T cell homeostasis, autoimmunity, and antitumor immunity. J Exp Med. 2017;214:1493-1507 pubmed publisher
    ..In this study, we have identified TANK-binding kinase 1 (TBK1), a master innate immune kinase, as an important regulator of DC function...
  33. Lin Y, Huang D, Chu C, Lin Y, Lin W. The tyrosine kinase Syk differentially regulates Toll-like receptor signaling downstream of the adaptor molecules TRAF6 and TRAF3. Sci Signal. 2013;6:ra71 pubmed publisher
    ..stimulates the production of type I interferons (IFNs) through a pathway that depends on TRAF3 and the kinase TBK1 (TANK-binding kinase-1)...
  34. Liu Y, Zeng L, Tian A, Bomkamp A, Rivera D, Gutman D, et al. Endoplasmic reticulum stress regulates the innate immunity critical transcription factor IRF3. J Immunol. 2012;189:4630-9 pubmed publisher
    ..Our results also suggest certain types of ER stress accomplish IRF3 phosphorylation by co-opting existing innate immune pathogen response pathways. These data have implications for diseases involving ER stress and type I IFN. ..
  35. Hasan M, Gonugunta V, Dobbs N, Ali A, Palchik G, Calvaruso M, et al. Chronic innate immune activation of TBK1 suppresses mTORC1 activity and dysregulates cellular metabolism. Proc Natl Acad Sci U S A. 2017;114:746-751 pubmed publisher
    ..GMP-AMP synthase-stimulator of interferon genes-TANK-binding kinase-interferon regulatory factor 3 (cGAS-STING-TBK1-IRF3) signaling pathway...
  36. Fernandes Alnemri T, Kang S, Anderson C, Sagara J, Fitzgerald K, Alnemri E. Cutting edge: TLR signaling licenses IRAK1 for rapid activation of the NLRP3 inflammasome. J Immunol. 2013;191:3995-9 pubmed publisher
    ..These findings define the pathways that lead to rapid NLRP3 activation and identify IRAK1 as a critical mediator of a transcription-independent,inflammasome-dependent early warning response to pathogenic infection. ..
  37. Farlik M, Rapp B, Marie I, Levy D, Jamieson A, Decker T. Contribution of a TANK-binding kinase 1-interferon (IFN) regulatory factor 7 pathway to IFN-?-induced gene expression. Mol Cell Biol. 2012;32:1032-43 pubmed publisher
    ..control of the Gbp2 gene required the presence and basal activity of the S/T kinase TANK-binding kinase 1 (TBK1), whereas the binding of IRF7 to the Gbp2 promoter did not...
  38. Ye W, Hu M, Lei C, Zhou Q, Lin H, Sun M, et al. TRIM8 Negatively Regulates TLR3/4-Mediated Innate Immune Response by Blocking TRIF-TBK1 Interaction. J Immunol. 2017;199:1856-1864 pubmed publisher
    ..Our findings uncover an additional mechanism on the termination of TLR3/4-mediated inflammatory and innate immune responses. ..
  39. Wang F, Alain T, Szretter K, Stephenson K, Pol J, Atherton M, et al. S6K-STING interaction regulates cytosolic DNA-mediated activation of the transcription factor IRF3. Nat Immunol. 2016;17:514-522 pubmed publisher
    ..the kinase domain, but not the kinase function, of S6K1 was required for the S6K1-STING interaction and that the TBK1 critically promoted this process...
  40. Stanley S, Johndrow J, Manzanillo P, Cox J. The Type I IFN response to infection with Mycobacterium tuberculosis requires ESX-1-mediated secretion and contributes to pathogenesis. J Immunol. 2007;178:3143-52 pubmed
    ..We propose that the ESX-1 secretion system secretes effectors into the cytosol of infected macrophages, thereby triggering the type I IFN response for the manipulation of host immunity. ..
  41. Verpooten D, Ma Y, Hou S, Yan Z, He B. Control of TANK-binding kinase 1-mediated signaling by the gamma(1)34.5 protein of herpes simplex virus 1. J Biol Chem. 2009;284:1097-105 pubmed publisher
    TANK-binding kinase 1 (TBK1) is a key component of Toll-like receptor-dependent and -independent signaling pathways. In response to microbial components, TBK1 activates interferon regulatory factor 3 (IRF3) and cytokine expression...
  42. Bruni D, Sebastia J, Dunne S, Schröder M, Butler M. A novel IRAK1-IKK? signaling axis limits the activation of TAK1-IKK? downstream of TLR3. J Immunol. 2013;190:2844-56 pubmed publisher
    ..Recently, IKK? and TANK-binding kinase 1 (TBK1) were reported to limit activation of the NF-?B pathway downstream of IL-1R, TNFR1, and TLRs...
  43. Zhang L, Mo J, Swanson K, Wen H, Petrucelli A, Gregory S, et al. NLRC3, a member of the NLR family of proteins, is a negative regulator of innate immune signaling induced by the DNA sensor STING. Immunity. 2014;40:329-41 pubmed publisher
    ..is an intracellular DNA sensor that induces type I interferon through its interaction with TANK-binding kinase 1 (TBK1)...
  44. Deng W, Shi M, Han M, Zhong J, Li Z, Li W, et al. Negative regulation of virus-triggered IFN-beta signaling pathway by alternative splicing of TBK1. J Biol Chem. 2008;283:35590-7 pubmed publisher
    ..Induction of Type I IFNs is a central event in antiviral responses and must be tightly controlled. The protein kinase TBK1 is critically involved in virus-triggered type I IFN signaling...
  45. Hasan M, Fermaintt C, Gao N, Sakai T, Miyazaki T, Jiang S, et al. Cytosolic Nuclease TREX1 Regulates Oligosaccharyltransferase Activity Independent of Nuclease Activity to Suppress Immune Activation. Immunity. 2015;43:463-74 pubmed publisher
    ..This function of the TREX1 C terminus suggests a potential therapeutic option for TREX1-fs mutant-associated diseases. ..
  46. Yu J, Zhou X, Chang M, Nakaya M, Chang J, Xiao Y, et al. Regulation of T-cell activation and migration by the kinase TBK1 during neuroinflammation. Nat Commun. 2015;6:6074 pubmed publisher
    ..Here we show that T-cell-specific ablation of the kinase TBK1 promotes T-cell activation but causes retention of effector T cells in the draining lymph node in a ..
  47. Kang H, Cheong W, Park J, Ryu S, Cho H, Youn H, et al. Murine gammaherpesvirus 68 encoding open reading frame 11 targets TANK binding kinase 1 to negatively regulate the host type I interferon response. J Virol. 2014;88:6832-46 pubmed publisher
    ..MHV-68 ORF11 decreased IFN-? promoter activation by various factors, the signaling of which converges on TBK1-IRF3 activation. MHV-68 ORF11 directly interacted with both overexpressed and endogenous TBK1 but not with IRF3...
  48. Nakatsu Y, Matsuoka M, Chang T, Otsuki N, Noda M, Kimura H, et al. Functionally distinct effects of the C-terminal regions of IKK? and TBK1 on type I IFN production. PLoS ONE. 2014;9:e94999 pubmed publisher
    Inhibitor of ?B kinase ? (IKK?) and TANK binding kinase 1 (TBK1), so-called non-canonical IKKs or IKK-related kinases, are involved in the cellular innate immunity by inducing type I IFNs...
  49. Song G, Liu B, Li Z, Wu H, Wang P, Zhao K, et al. E3 ubiquitin ligase RNF128 promotes innate antiviral immunity through K63-linked ubiquitination of TBK1. Nat Immunol. 2016;17:1342-1351 pubmed publisher
    b>TBK1 is essential for interferon-? (IFN-?) production and innate antiviral immunity. Here we identified the T cell anergy-related E3 ubiquitin ligase RNF128 as a positive regulator of TBK1 activation...
  50. Oganesyan G, Saha S, Pietras E, Guo B, Miyahira A, Zarnegar B, et al. IRF3-dependent type I interferon response in B cells regulates CpG-mediated antibody production. J Biol Chem. 2008;283:802-8 pubmed
    ..on the transcription factor IRF3, but similar to dendritic cells this pathway was independent of the IRF3 kinase TBK1. Utilizing type I IFN receptor-deficient mice, we were able to demonstrate that this IFN pathway enhanced Syndecan-..
  51. Smith H, Liu X, Dai L, Goh E, Chan A, Xi J, et al. The role of TBK1 and IKKε in the expression and activation of Pellino 1. Biochem J. 2011;434:537-48 pubmed publisher
    ..is prevented by inhibition of the IKK [IκB (inhibitor of nuclear factor κB) kinase]-related protein kinases, TBK1 {TANK [TRAF (tumour-necrosis-factor-receptor-associated factor)-associated nuclear factor κB activator]-binding ..
  52. Lee K, Xu S, Kang Z, Huo J, Huang M, Liu D, et al. Bruton's tyrosine kinase phosphorylates Toll-like receptor 3 to initiate antiviral response. Proc Natl Acad Sci U S A. 2012;109:5791-6 pubmed publisher
    ..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.
  53. Everts B, Amiel E, Huang S, Smith A, Chang C, Lam W, et al. TLR-driven early glycolytic reprogramming via the kinases TBK1-IKK? supports the anabolic demands of dendritic cell activation. Nat Immunol. 2014;15:323-32 pubmed publisher
    ..Signaling via the kinases TBK1, IKK? and Akt was essential for the TLR-induced increase in glycolysis by promoting the association of the ..
  54. Civas A, Genin P, Morin P, Lin R, Hiscott J. Promoter organization of the interferon-A genes differentially affects virus-induced expression and responsiveness to TBK1 and IKKepsilon. J Biol Chem. 2006;281:4856-66 pubmed
    ..IRF-7, which are activated by phosphorylation during viral infection by the IKK-related serine/threonine kinases TBK1 and IkappaB kinase epsilon (IKKepsilon)...
  55. Delhase M, Kim S, Lee H, Naiki Ito A, Chen Y, Ahn E, et al. TANK-binding kinase 1 (TBK1) controls cell survival through PAI-2/serpinB2 and transglutaminase 2. Proc Natl Acad Sci U S A. 2012;109:E177-86 pubmed publisher
    ..Genetic studies in mice have identified the I?B kinase-related kinase TANK-binding kinase 1 (TBK1; also called NAK or T2K) as an additional regulatory molecule that promotes survival downstream of TNF, but the ..
  56. Chessler A, Ferreira L, Chang T, Fitzgerald K, Burleigh B. A novel IFN regulatory factor 3-dependent pathway activated by trypanosomes triggers IFN-beta in macrophages and fibroblasts. J Immunol. 2008;181:7917-24 pubmed
    ..In this study, we report that signaling through TBK1 and IFN regulatory factor 3 is required for T. cruzi-mediated expression of IFN-beta...
  57. Du M, Liu J, Chen X, Xie Y, Yuan C, Xiang Y, et al. Casein kinase II controls TBK1/IRF3 activation in IFN response against viral infection. J Immunol. 2015;194:4477-88 pubmed publisher
    By sensing viral nucleic acids, host innate receptors elicit signaling pathways converging on TBK1-IFN regulatory factor (IRF)3 axis in mediating IFN-αβ induction and defense mechanisms...
  58. Tsuzuki S, Tachibana M, Hemmi M, Yamaguchi T, Shoji M, Sakurai F, et al. TANK-binding kinase 1-dependent or -independent signaling elicits the cell-type-specific innate immune responses induced by the adenovirus vector. Int Immunol. 2016;28:105-15 pubmed publisher
    ..the impacts of viral nucleic acids on innate immune responses in vivo, we administered transgene-expressing Adv to Tbk1-deficient mice...
  59. Abe T, Barber G. Cytosolic-DNA-mediated, STING-dependent proinflammatory gene induction necessitates canonical NF-?B activation through TBK1. J Virol. 2014;88:5328-41 pubmed publisher
    ..Furthermore, TANK-binding kinase 1 (TBK1) associated with STING was found to facilitate dsDNA-mediated canonical activation of NF-?B as well as IRF3 to ..
  60. Zhang M, Wang L, Zhao X, Zhao K, Meng H, Zhao W, et al. TRAF-interacting protein (TRIP) negatively regulates IFN-? production and antiviral response by promoting proteasomal degradation of TANK-binding kinase 1. J Exp Med. 2012;209:1703-11 pubmed
    TANK-binding kinase 1 (TBK1) plays an essential role in Toll-like receptor (TLR)- and retinoic acid-inducible gene I (RIG-I)-mediated induction of type I interferon (IFN; IFN-?/?) and host antiviral responses...
  61. Lam E, Stein S, Falck Pedersen E. Adenovirus detection by the cGAS/STING/TBK1 DNA sensing cascade. J Virol. 2014;88:974-81 pubmed publisher
    ..Short hairpin RNA (shRNA) lentiviral vectors targeting TBK1, STING, and cGAS were established in murine MS1 endothelial and RAW 264.7 macrophage cell lines...
  62. Pedros C, Zhang Y, Hu J, Choi Y, Canonigo Balancio A, Yates J, et al. A TRAF-like motif of the inducible costimulator ICOS controls development of germinal center TFH cells via the kinase TBK1. Nat Immunol. 2016;17:825-33 pubmed publisher
    ..However, a signaling pathway unique to ICOS has not been identified. We found here that the kinase TBK1 associated with ICOS via a conserved motif, IProx, that shares homology with the tumor-necrosis-factor receptor (..
  63. Shu C, Sankaran B, Chaton C, Herr A, Mishra A, Peng J, et al. Structural insights into the functions of TBK1 in innate antimicrobial immunity. Structure. 2013;21:1137-48 pubmed publisher
    Tank-binding kinase 1 (TBK1) is a serine/threonine protein-kinase mediating innate antimicrobial immunity. TBK1 is involved in the signaling of TLRs, RLRs, and STING-mediated sensing of cytosolic DNA...
  64. Parvatiyar K, Zhang Z, Teles R, Ouyang S, Jiang Y, Iyer S, et al. The helicase DDX41 recognizes the bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I interferon immune response. Nat Immunol. 2012;13:1155-61 pubmed publisher
    ..c-di-GMP) or cyclic di-AMP (c-di-AMP) is dependent on a signaling axis that involves the adaptor STING, the kinase TBK1 and the transcription factor IRF3...
  65. Deng K, Wang A, Ji Y, Zhang X, Fang J, Zhang Y, et al. Suppressor of IKK? is an essential negative regulator of pathological cardiac hypertrophy. Nat Commun. 2016;7:11432 pubmed publisher
    ..pathway, attenuates pathological cardiac hypertrophy in rodents and non-human primates in a TANK-binding kinase 1 (TBK1)/AKT-dependent manner...
  66. Munitic I, Giardino Torchia M, Meena N, Zhu G, Li C, Ashwell J. Optineurin insufficiency impairs IRF3 but not NF-κB activation in immune cells. J Immunol. 2013;191:6231-40 pubmed publisher
    ..Importantly, Optn(470T) mice produced less IFN-β upon LPS challenge. Therefore, endogenous optineurin is dispensable for NF-κB activation but necessary for optimal IRF3 activation in immune cells. ..
  67. Bakshi S, Taylor J, Strickson S, McCartney T, Cohen P. Identification of TBK1 complexes required for the phosphorylation of IRF3 and the production of interferon ?. Biochem J. 2017;474:1163-1174 pubmed publisher
    ..respectively, triggering the activation of TANK (TRAF family member-associated NF-?B activator)-binding kinase 1 (TBK1) complexes, the phosphorylation of interferon regulatory factor 3 (IRF3) and transcription of the interferon ? (IFN?..
  68. Polumuri S, Jayakar G, Shirey K, Roberts Z, Perkins D, Pitha P, et al. Transcriptional regulation of murine IL-33 by TLR and non-TLR agonists. J Immunol. 2012;189:50-60 pubmed publisher
    ..Together, these studies greatly extend what is currently known about the regulation of IL-33 induction in macrophages stimulated by bacterial and viral agonists that engage distinct innate immune signaling pathways. ..
  69. Chiba S, Baghdadi M, Akiba H, Yoshiyama H, Kinoshita I, Dosaka Akita H, et al. Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nat Immunol. 2012;13:832-42 pubmed publisher
    ..Our findings define a mechanism whereby tumor microenvironments suppress antitumor immunity mediated by nucleic acids. ..
  70. Kim S, Lee K, Chin C, Ng S, Pereira N, Xu S, et al. DOK3 is required for IFN-? production by enabling TRAF3/TBK1 complex formation and IRF3 activation. J Immunol. 2014;193:840-8 pubmed publisher
    ..DOK3 was shown to bind TBK1 and was required for its activation...
  71. Mowers J, Uhm M, Reilly S, Simon J, Leto D, Chiang S, et al. Inflammation produces catecholamine resistance in obesity via activation of PDE3B by the protein kinases IKK? and TBK1. elife. 2013;2:e01119 pubmed publisher
    ..state involving the NF?B pathway, resulting in persistent elevation of the noncanonical I?B kinases IKK? and TBK1. In this study, we report that these kinases attenuate ?-adrenergic signaling in white adipose tissue...
  72. Gabhann J, Higgs R, Brennan K, Thomas W, Damen J, Ben Larbi N, et al. Absence of SHIP-1 results in constitutive phosphorylation of tank-binding kinase 1 and enhanced TLR3-dependent IFN-beta production. J Immunol. 2010;184:2314-20 pubmed publisher
    ..Further dissection of the IFN-beta pathway implicates TANK-binding kinase 1 (TBK1) as the target for SHIP-1...
  73. Chen H, Sun H, You F, Sun W, Zhou X, Chen L, et al. Activation of STAT6 by STING is critical for antiviral innate immunity. Cell. 2011;147:436-46 pubmed publisher
    ..named MITA/ERIS) to recruit STAT6 to the endoplasmic reticulum, leading to STAT6 phosphorylation on Ser(407) by TBK1 and Tyr(641), independent of JAKs...
  74. Da Q, Yang X, Xu Y, Gao G, Cheng G, Tang H. TANK-binding kinase 1 attenuates PTAP-dependent retroviral budding through targeting endosomal sorting complex required for transport-I. J Immunol. 2011;186:3023-30 pubmed publisher
    ..In this study, we demonstrated that TANK-binding kinase 1 (TBK1) directly interacted with VPS37C, a subunit of endosomal sorting complex required for transport-I (ESCRT-I) in the ..