TBK1

Summary

Gene Symbol: TBK1
Description: TANK binding kinase 1
Alias: FTDALS4, NAK, T2K, serine/threonine-protein kinase TBK1, NF-kB-activating kinase, NF-kappa-B-activating kinase
Species: human

Top Publications

  1. ncbi IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway
    Katherine A Fitzgerald
    Division of Infectious Disease and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Nat Immunol 4:491-6. 2003
  2. ncbi Molecular and cellular mechanisms of DNA vaccines
    Cevayir Coban
    Laboratory of Host Defense, Immunology Frontier Research Center, World Premier Institute for Immunology, Suita, Osaka, Japan
    Hum Vaccin 4:453-6. 2008
  3. doi The major outer membrane protein of a periodontopathogen induces IFN-beta and IFN-stimulated genes in monocytes via lipid raft and TANK-binding kinase 1/IFN regulatory factor-3
    Sung Hoon Lee
    Department of Oral Microbiology and Immunology, Seoul National University, Seoul, Republic of Korea
    J Immunol 182:5823-35. 2009
  4. doi The role of TBK1 and IKKε in the expression and activation of Pellino 1
    Hilary Smith
    MRC Protein Phosphorylation Unit, The Sir James Black Centre, College of Life Sciences, University of Dundee, Dundee, UK
    Biochem J 434:537-48. 2011
  5. pmc Molecular basis of Tank-binding kinase 1 activation by transautophosphorylation
    Xiaolei Ma
    Departments of Structural Biology, Genentech, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 109:9378-83. 2012
  6. pmc Human T cell lymphotropic virus 1 manipulates interferon regulatory signals by controlling the TAK1-IRF3 and IRF4 pathways
    Shunsuke Suzuki
    Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930 0194, Japan
    J Biol Chem 285:4441-6. 2010
  7. ncbi Constitutive and interleukin-1-inducible phosphorylation of p65 NF-{kappa}B at serine 536 is mediated by multiple protein kinases including I{kappa}B kinase (IKK)-{alpha}, IKK{beta}, IKK{epsilon}, TRAF family member-associated (TANK)-binding kinase 1 (TBK
    Holger Buss
    Institute of Pharmacology, Medical School Hannover, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
    J Biol Chem 279:55633-43. 2004
  8. pmc The pathogenic NY-1 hantavirus G1 cytoplasmic tail inhibits RIG-I- and TBK-1-directed interferon responses
    Peter J Alff
    Molecular and Cellular Biology Graduate Program, SUNY at Stony Brook, Stony Brook, NY 11794, USA
    J Virol 80:9676-86. 2006
  9. pmc NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase
    J L Pomerantz
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    EMBO J 18:6694-704. 1999
  10. pmc Deficiency of T2K leads to apoptotic liver degeneration and impaired NF-kappaB-dependent gene transcription
    M Bonnard
    Amgen Institute, Ontario Cancer Institute and the Department of Medical Biophysics, University of Toronto, 620 University Avenue, Toronto, Ontario, Canada
    EMBO J 19:4976-85. 2000

Research Grants

  1. Innate Immunity: Signal Transduction and Interferon Gene Regulation
    THOMAS P MANIATIS; Fiscal Year: 2010
  2. Zhijian J Chen; Fiscal Year: 2015
  3. ALBERT SIDNEY BALDWIN; Fiscal Year: 2014
  4. Role of a novel IKK-related kinase in inflammation
    SUSAN ELAINE SWEENEY; Fiscal Year: 2010
  5. Regulation of Type I Interferon Gene Expression in the Innate Immune Response
    Katherine A Fitzgerald; Fiscal Year: 2012
  6. The Role of Ubiquitination on TBK1 Function
    Roosevelt Boursiquot; Fiscal Year: 2010
  7. Shen Ying Zhang; Fiscal Year: 2016
  8. Andrei E Medvedev; Fiscal Year: 2014
  9. Martin E Dorf; Fiscal Year: 2015
  10. Ha Linh Vu; Fiscal Year: 2016

Detail Information

Publications225 found, 100 shown here

  1. ncbi IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway
    Katherine A Fitzgerald
    Division of Infectious Disease and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Nat Immunol 4:491-6. 2003
    ..that the noncanonical IkappaB kinase homologs, IkappaB kinase-epsilon (IKKepsilon) and TANK-binding kinase-1 (TBK1), which were previously implicated in NF-kappaB activation, are also essential components of the IRF3 signaling ..
  2. ncbi Molecular and cellular mechanisms of DNA vaccines
    Cevayir Coban
    Laboratory of Host Defense, Immunology Frontier Research Center, World Premier Institute for Immunology, Suita, Osaka, Japan
    Hum Vaccin 4:453-6. 2008
    ..was reported that the adjuvant effect of plasmid DNA is mediated by its double-stranded structure, which activates TBK1-dependent innate immune signaling pathways in the absence of TLRs...
  3. doi The major outer membrane protein of a periodontopathogen induces IFN-beta and IFN-stimulated genes in monocytes via lipid raft and TANK-binding kinase 1/IFN regulatory factor-3
    Sung Hoon Lee
    Department of Oral Microbiology and Immunology, Seoul National University, Seoul, Republic of Korea
    J Immunol 182:5823-35. 2009
    ..Experiments using specific small interfering RNA showed that MspTL activated TANK-binding kinase 1 (TBK1), but not inducible IkappaB kinase (IKKi)...
  4. doi The role of TBK1 and IKKε in the expression and activation of Pellino 1
    Hilary Smith
    MRC Protein Phosphorylation Unit, The Sir James Black Centre, College of Life Sciences, University of Dundee, Dundee, UK
    Biochem J 434:537-48. 2011
    ..and 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 ..
  5. pmc Molecular basis of Tank-binding kinase 1 activation by transautophosphorylation
    Xiaolei Ma
    Departments of Structural Biology, Genentech, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 109:9378-83. 2012
    ..the biology of this key immunological factor have intensified recently as growing evidence implicates aberrant TBK1 activity in a variety of autoimmune diseases and cancers...
  6. pmc Human T cell lymphotropic virus 1 manipulates interferon regulatory signals by controlling the TAK1-IRF3 and IRF4 pathways
    Shunsuke Suzuki
    Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930 0194, Japan
    J Biol Chem 285:4441-6. 2010
    ..Activation of IRF3 and IRF3-dependent gene expressions was dependent on TAK1 and TANK-binding kinase 1 (TBK1)...
  7. ncbi Constitutive and interleukin-1-inducible phosphorylation of p65 NF-{kappa}B at serine 536 is mediated by multiple protein kinases including I{kappa}B kinase (IKK)-{alpha}, IKK{beta}, IKK{epsilon}, TRAF family member-associated (TANK)-binding kinase 1 (TBK
    Holger Buss
    Institute of Pharmacology, Medical School Hannover, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
    J Biol Chem 279:55633-43. 2004
    ..Peak 1 represents an unknown kinase, whereas peak 2 contained IKKalpha, IKKbeta, IKKepsilon, and TBK1. Overexpressed IKKepsilon and TBK1 phosphorylate Ser-536 in vivo and in vitro...
  8. pmc The pathogenic NY-1 hantavirus G1 cytoplasmic tail inhibits RIG-I- and TBK-1-directed interferon responses
    Peter J Alff
    Molecular and Cellular Biology Graduate Program, SUNY at Stony Brook, Stony Brook, NY 11794, USA
    J Virol 80:9676-86. 2006
    ....
  9. pmc NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase
    J L Pomerantz
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    EMBO J 18:6694-704. 1999
    ..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...
  10. pmc Deficiency of T2K leads to apoptotic liver degeneration and impaired NF-kappaB-dependent gene transcription
    M Bonnard
    Amgen Institute, Ontario Cancer Institute and the Department of Medical Biophysics, University of Toronto, 620 University Avenue, Toronto, Ontario, Canada
    EMBO J 19:4976-85. 2000
    ..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...
  11. ncbi Triggering the interferon antiviral response through an IKK-related pathway
    Sonia Sharma
    Lady Davis Institute for Medical Research Jewish General Hospital, Departments of Microbiology and Immunology and Medicine, McGill University, Montreal, Quebec H3T 1E2, Canada
    Science 300:1148-51. 2003
    ..These studies illustrate an essential role for an IKK-related kinase pathway in triggering the host antiviral response to viral infection...
  12. ncbi Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kappa B and IFN-regulatory factor-3, in the Toll-like re
    Shintaro Sato
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Japan
    J Immunol 171:4304-10. 2003
    ..Moreover, the association between TRIF and TBK1 appeared to require the kinase activity of TBK1, as well as phosphorylation of TRIF...
  13. pmc Identification of NAP1, a regulatory subunit of IkappaB kinase-related kinases that potentiates NF-kappaB signaling
    Fumitaka Fujita
    Department of Biochemistry and Cell Biology, Graduate School of Medicine, Nagoya City University, Mizuho ku, Nagoya 467 8601, Japan
    Mol Cell Biol 23:7780-93. 2003
    The IkappaB kinase (IKK)-related kinase NAK (also known as TBK or T2K) contributes to the activation of NF-kappaB-dependent gene expression...
  14. ncbi A CRM1-dependent nuclear export pathway is involved in the regulation of IRF-5 subcellular localization
    Rongtuan Lin
    Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec H3T 1E2, Canada
    J Biol Chem 280:3088-95. 2005
    ..IKK-related kinases TBK1 and IKKepsilon have been shown to phosphorylate and activate IRF-3 and IRF-7, leading to the production of type 1 ..
  15. ncbi The interferon regulatory factor, IRF5, is a central mediator of toll-like receptor 7 signaling
    Annett Schoenemeyer
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    J Biol Chem 280:17005-12. 2005
    ..IRF5 and IRF7, therefore, emerge from these studies as critical mediators of TLR7 signaling...
  16. ncbi Interaction between the HCV NS3 protein and the host TBK1 protein leads to inhibition of cellular antiviral responses
    Motoyuki Otsuka
    Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Japan
    Hepatology 41:1004-12. 2005
    ..studies suggest that a TIR domain-containing adaptor protein, TRIF, and two protein kinases, TANK-binding kinase-1 (TBK1) and IkappaB kinase-epsilon (IKKepsilon), play essential roles in TLR3-mediated IFN-beta production through the ..
  17. ncbi IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction
    Taro Kawai
    Exploratory Research for Advanced Technology, Japan Science and Technology Agency
    Nat Immunol 6:981-8. 2005
    ..b>TBK1 and IKKi protein kinases were required for the IPS-1-mediated interferon induction...
  18. ncbi VISA is an adapter protein required for virus-triggered IFN-beta signaling
    Liang Guo Xu
    Department of Immunology, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, Colorado 80206, USA
    Mol Cell 19:727-40. 2005
    ..These findings suggest that VISA is critically involved in both virus-triggered TLR3-independent and TLR3-mediated antiviral IFN signaling...
  19. pmc Viral targeting of the interferon-{beta}-inducing Traf family member-associated NF-{kappa}B activator (TANK)-binding kinase-1
    Gunhild Unterstab
    Robert Koch Institute, FG12, Nordufer 20, 13353 Berlin, Germany
    Proc Natl Acad Sci U S A 102:13640-5. 2005
    ..Thus, our findings provide evidence for a previously undescribed mechanism by which a viral protein interferes with the induction of the antiviral IFN cascade...
  20. pmc SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus-triggered IRF-3 activation pathways
    Jun Huang
    College of Life Sciences, Peking University, Beijing, China
    EMBO J 24:4018-28. 2005
    ..IKKepsilon and TBK1 are two IKK-related kinases critically involved in virus- and TLR3-triggered activation of IRF-3...
  21. ncbi The Ret finger protein inhibits signaling mediated by the noncanonical and canonical IkappaB kinase family members
    Jikun Zha
    Department of Cell Biology and Genetics, College of Life Sciences, Peking University, Beijing, China
    J Immunol 176:1072-80. 2006
    ..Taken together, our findings suggest that RFP negatively regulates signaling involved in the antiviral response and inflammation by targeting the IKKs...
  22. pmc Hsp90 regulates activation of interferon regulatory factor 3 and TBK-1 stabilization in Sendai virus-infected cells
    Kai Yang
    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, People s Republic of China
    Mol Biol Cell 17:1461-71. 2006
    ..The protein kinase TBK1 is a key regulator inducing phosphorylation of IRF3...
  23. ncbi Nuclear accumulation of cRel following C-terminal phosphorylation by TBK1/IKK epsilon
    Jennifer Harris
    Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, 3755 chemin de la Cote Sainte Catherine, Montreal, Quebec, Canada
    J Immunol 177:2527-35. 2006
    ..b>TBK1 and IKKepsilon were recently described as essential regulators of IFN gene activation through direct ..
  24. ncbi RalB GTPase-mediated activation of the IkappaB family kinase TBK1 couples innate immune signaling to tumor cell survival
    Yuchen Chien
    Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA
    Cell 127:157-70. 2006
    ..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 ..
  25. ncbi Modulation of the interferon antiviral response by the TBK1/IKKi adaptor protein TANK
    Beichu Guo
    Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California 90095, USA
    J Biol Chem 282:11817-26. 2007
    ..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...
  26. ncbi Interferon regulatory factor 3 is regulated by a dual phosphorylation-dependent switch
    Daniel Panne
    Department of Biological Chemistry and Molecular Pharmacology, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 282:22816-22. 2007
    ..IRF-3 is activated through phosphorylation by the kinases IKK epsilon and/or TBK1. Phosphorylation results in IRF-3 dimerization and removal of an autoinhibitory structure to allow interaction with ..
  27. pmc SINTBAD, a novel component of innate antiviral immunity, shares a TBK1-binding domain with NAP1 and TANK
    Grigory Ryzhakov
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    EMBO J 26:3180-90. 2007
    ..Activation of IRF3 requires its phosphorylation by TBK1 (TANK-binding kinase) or IKKi (inhibitor of nuclear factor kappaB kinase, inducible)...
  28. pmc Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes
    Fumiyo Ikeda
    Institute of Biochemistry II, Goethe University Medical School, Frankfurt, Germany
    EMBO J 26:3451-62. 2007
    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...
  29. ncbi Lipopolysaccharide-mediated interferon regulatory factor activation involves TBK1-IKKepsilon-dependent Lys(63)-linked polyubiquitination and phosphorylation of TANK/I-TRAF
    Jean Stéphane Gatot
    Interdisciplinary Cluster for Applied Genoproteomics, Medical Chemistry, and Virology Immunology units, University of Liege, Sart Tilman, 4000 Liege, Belgium
    J Biol Chem 282:31131-46. 2007
    Type I interferon gene induction relies on IKK-related kinase TBK1 and IKKepsilon-mediated phosphorylations of IRF3/7 through the Toll-like receptor-dependent signaling pathways...
  30. ncbi DUBA: a deubiquitinase that regulates type I interferon production
    Nobuhiko Kayagaki
    Department of Physiological Chemistry, Genentech, South San Francisco, CA 94080, USA
    Science 318:1628-32. 2007
    ..A discrete ubiquitin interaction motif within DUBA was required for efficient deubiquitination of TRAF3 and optimal suppression of IFN-I. Our data identify DUBA as a negative regulator of innate immune responses...
  31. doi Enhanced binding of TBK1 by an optineurin mutant that causes a familial form of primary open angle glaucoma
    Simon Morton
    MRC Protein Phosphorylation Unit, College of Life Sciences, Sir James Black Centre, University of Dundee, Dundee DD1 5EH, Scotland, UK
    FEBS Lett 582:997-1002. 2008
    TANK-binding kinase 1 (TBK1) was identified as a binding partner for Optineurin (OPTN) in two-hybrid screens, an interaction confirmed by overexpression/immunoprecipitation experiments in HEK293 cells and by coimmunoprecipitation of ..
  32. doi Are the IKKs and IKK-related kinases TBK1 and IKK-epsilon similarly activated?
    Tieu Lan Chau
    Interdisciplinary Cluster for Applied Genoproteomics, University of Liege, Sart Tilman, 4000 Liege, Belgium
    Trends Biochem Sci 33:171-80. 2008
    The IkappaB kinases (IKKs) IKK-alpha and IKK-beta, and the IKK-related kinases TBK1 and IKK-epsilon, have essential roles in innate immunity through signal-induced activation of NF-kappaB, IRF3 and IRF7, respectively...
  33. pmc The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response
    Didier Soulat
    Department of Infection Biology, Max F Perutz Laboratories, University of Vienna, Vienna, Austria
    EMBO J 27:2135-46. 2008
    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...
  34. pmc The NY-1 hantavirus Gn cytoplasmic tail coprecipitates TRAF3 and inhibits cellular interferon responses by disrupting TBK1-TRAF3 complex formation
    Peter J Alff
    Molecular and Cellular Biology Graduate Program, SUNY at Stony Brook, Stony Brook, NY 11794, USA
    J Virol 82:9115-22. 2008
    ..Expression of the cytoplasmic tail of the pathogenic NY-1 hantavirus Gn protein is sufficient to inhibit RIG-I- and TBK1-directed IFN responses...
  35. pmc The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response
    Constantin S Friedman
    Immunology Institute, Mount Sinai School of Medicine, Box 1630, One Gustave L Levy Place, New York, New York 10029, USA
    EMBO Rep 9:930-6. 2008
    ..CYLD removes polyubiquitin chains from RIG-I as well as from TANK binding kinase 1 (TBK1), the kinase that phosphorylates IRF3, coincident with an inhibition of the IRF3 signalling pathway...
  36. pmc Ebola virus protein VP35 impairs the function of interferon regulatory factor-activating kinases IKKepsilon and TBK-1
    Kathleen C Prins
    Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Virol 83:3069-77. 2009
    ....
  37. doi The IKK-related kinases: from innate immunity to oncogenesis
    Jean François Clément
    Faculte de Pharmacie, Universite de Montreal, C P 6128, Succursale Centre Ville, Montreal, Quebec, Canada H3C 3J7
    Cell Res 18:889-99. 2008
    ..has been highly influenced by the discovery of the IkappaB kinase (IKK)-related kinases, TANK Binding Kinase 1 (TBK1) and IKKi, which regulate the activity of interferon regulatory factor (IRF)-3/IRF-7 and NF-kappaB transcription ..
  38. pmc Use of the pharmacological inhibitor BX795 to study the regulation and physiological roles of TBK1 and IkappaB kinase epsilon: a distinct upstream kinase mediates Ser-172 phosphorylation and activation
    Kristopher Clark
    MRC Protein Phosphorylation Unit, College of Life Sciences, Sir James Black Centre, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom
    J Biol Chem 284:14136-46. 2009
    TANK-binding kinase 1 (TBK1) and IkappaB kinase epsilon (IKKepsilon) regulate the production of Type 1 interferons during bacterial and viral infection, but the lack of useful pharmacological inhibitors has hampered progress in ..
  39. pmc ISG56 is a negative-feedback regulator of virus-triggered signaling and cellular antiviral response
    Ying Li
    College of Life Sciences, Wuhan University, Wuhan 430072, China
    Proc Natl Acad Sci U S A 106:7945-50. 2009
    ..coimmunoprecipitation experiments indicated that ISG56 disrupted the interactions between MITA and VISA or TBK1, two components in the virus-triggered IFN signaling pathways...
  40. doi The TBK1 adaptor and autophagy receptor NDP52 restricts the proliferation of ubiquitin-coated bacteria
    Teresa L M Thurston
    Medical Research Council Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Cambridge, UK
    Nat Immunol 10:1215-21. 2009
    ..proteins can accumulate on the surface of such bacteria, and bacterial growth is restricted by Tank-binding kinase (TBK1)...
  41. pmc Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1
    David A Barbie
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115 USA
    Nature 462:108-12. 2009
    ..interference to detect synthetic lethal partners of oncogenic KRAS and found that the non-canonical IkappaB kinase TBK1 was selectively essential in cells that contain mutant KRAS...
  42. pmc TAX1BP1 and A20 inhibit antiviral signaling by targeting TBK1-IKKi kinases
    Kislay Parvatiyar
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, Florida 33136, USA
    J Biol Chem 285:14999-5009. 2010
    ..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 ..
  43. pmc Emerging roles for the non-canonical IKKs in cancer
    R R Shen
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Oncogene 30:631-41. 2011
    The IκB Kinase (IKK)-related kinases TBK1 and IKKɛ have essential roles as regulators of innate immunity by modulating interferon and NF-κB signaling. Recent work has also implicated these non-canonical IKKs in malignant transformation...
  44. doi Akt contributes to activation of the TRIF-dependent signaling pathways of TLRs by interacting with TANK-binding kinase 1
    Sun Myung Joung
    School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea
    J Immunol 186:499-507. 2011
    ..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...
  45. pmc PLP2 of mouse hepatitis virus A59 (MHV-A59) targets TBK1 to negatively regulate cellular type I interferon signaling pathway
    Gang Wang
    Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    PLoS ONE 6:e17192. 2011
    ....
  46. pmc IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by direct phosphorylation
    Xiaoduo Xie
    Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 108:6474-9. 2011
    ..Here we show that the atypical IκB kinase ε and TANK-binding kinase 1 (IKKε/TBK1) phosphorylate AKT on both the hydrophobic motif and the activation loop in a manner dependent on PI3K signaling...
  47. pmc Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth
    Philipp Wild
    Frankfurt Institute for Molecular Life Sciences and Institute of Biochemistry II, Goethe University School of Medicine, Frankfurt Main, Germany
    Science 333:228-33. 2011
    ..The protein kinase TANK binding kinase 1 (TBK1) phosphorylated optineurin on serine-177, enhancing LC3 binding affinity and autophagic clearance of cytosolic ..
  48. pmc E3 ubiquitin ligase CHIP facilitates Toll-like receptor signaling by recruiting and polyubiquitinating Src and atypical PKC{zeta}
    Mingjin Yang
    Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai200433, China
    J Exp Med 208:2099-112. 2011
    ..These findings suggest that CHIP facilitates the formation of a TLR signaling complex by recruiting, ubiquitinating, and activating Src and PKCζ...
  49. pmc Functional dissection of the TBK1 molecular network
    Adriana Goncalves
    CeMM Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria
    PLoS ONE 6:e23971. 2011
    TANK-binding kinase 1 (TBK1) and inducible IκB-kinase (IKK-i) are central regulators of type-I interferon induction...
  50. doi MIP-T3 is a negative regulator of innate type I IFN response
    Ming Him James Ng
    Department of Biochemistry, The University of Hong Kong, Pokfulam, Hong Kong, China
    J Immunol 187:6473-82. 2011
    ..Overexpression of MIP-T3 inhibited RIG-I-, MDA5-, VISA-, TBK1-, and IKKε-induced transcriptional activity mediated by IFN-stimulated response elements and IFN-β promoter...
  51. pmc NLRP4 negatively regulates type I interferon signaling by targeting the kinase TBK1 for degradation via the ubiquitin ligase DTX4
    Jun Cui
    The Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA
    Nat Immunol 13:387-95. 2012
    ..NLRP4 regulated the activation of type I interferon mediated by double-stranded RNA or DNA by targeting the kinase TBK1 for degradation...
  52. pmc STING specifies IRF3 phosphorylation by TBK1 in the cytosolic DNA signaling pathway
    Yasuo Tanaka
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9148, USA
    Sci Signal 5:ra20. 2012
    ..Here, we showed that STING stimulates phosphorylation of IRF3 by the kinase TBK1 (TANK-binding kinase 1) in an in vitro reconstitution system...
  53. pmc Proteomic profiling of the TRAF3 interactome network reveals a new role for the ER-to-Golgi transport compartments in innate immunity
    Wendy J van Zuylen
    Faculty of Pharmacy, Universite de Montreal, Montreal, Quebec Canada
    PLoS Pathog 8:e1002747. 2012
    ..and NF-κB -dependent promoters following viral infection and ectopic expression of MAVS and Tank-binding kinase-1 (TBK1)...
  54. pmc TRAF-interacting protein (TRIP) negatively regulates IFN-β production and antiviral response by promoting proteasomal degradation of TANK-binding kinase 1
    Meng Zhang
    Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Immunology, Shandong University School of Medicine, Shandong 250012, China
    J Exp Med 209:1703-11. 2012
    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-α/β) and host antiviral responses...
  55. pmc NEMO binds ubiquitinated TANK-binding kinase 1 (TBK1) to regulate innate immune responses to RNA viruses
    Lingyan Wang
    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 7:e43756. 2012
    ..b>TBK1 is a critical kinase implicated in RLR-dependent IFN transcription...
  56. doi Negative regulation of TBK1-mediated antiviral immunity
    Wei Zhao
    Department of Immunology, Shandong University School of Medicine, Jinan, Shandong 250012, China
    FEBS Lett 587:542-8. 2013
    TANK-binding kinase 1 (TBK1) plays pivotal roles in antiviral innate immunity. TBK1 mediates the activation of interferon regulatory factor (IRF) 3, leading to the induction of type I IFNs (IFN-α/β) following viral infections...
  57. pmc Structure and ubiquitination-dependent activation of TANK-binding kinase 1
    Daqi Tu
    Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA
    Cell Rep 3:747-58. 2013
    Upon stimulation by pathogen-associated inflammatory signals, TANK-binding kinase 1 (TBK1) induces type I interferon expression and modulates nuclear factor κB (NF-κB) signaling. Here, we describe the 2...
  58. pmc Human papillomavirus (HPV) upregulates the cellular deubiquitinase UCHL1 to suppress the keratinocyte's innate immune response
    Rezaul Karim
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    PLoS Pathog 9:e1003384. 2013
    ..This identifies UCHL1 as a negative regulator of PRR-induced immune responses and consequently its virus-increased expression as a strategy for hrHPV to persist...
  59. pmc A distinct role of Riplet-mediated K63-Linked polyubiquitination of the RIG-I repressor domain in human antiviral innate immune responses
    Hiroyuki Oshiumi
    Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita ku, Sapporo, Japan
    PLoS Pathog 9:e1003533. 2013
    ..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...
  60. ncbi NAK is an IkappaB kinase-activating kinase
    Y Tojima
    Department of Geriatric Research, National Institute for Longevity Sciences, Obu, Aichi, Japan
    Nature 404:778-82. 2000
    ..Here we describe an IKK-related kinase, named NAK (NF-kappaB-activating kinase), that can activate IKK through direct phosphorylation...
  61. ncbi IKK-i and TBK-1 are enzymatically distinct from the homologous enzyme IKK-2: comparative analysis of recombinant human IKK-i, TBK-1, and IKK-2
    Nandini Kishore
    Department of Arthritis and Inflammation Pharmacology, Discovery Research, Pharmacia Corporation, St Louis, Missouri 63167, USA
    J Biol Chem 277:13840-7. 2002
    ..Thus, although these IKKs are structurally similar, their enzymatic properties may provide insights into their unique functions...
  62. ncbi Association of the adaptor TANK with the I kappa B kinase (IKK) regulator NEMO connects IKK complexes with IKK epsilon and TBK1 kinases
    Alain Chariot
    Laboratory of Immunoregulation, NIAID, National Institutes of Health, Bethesda, Maryland 20892 1876, USA
    J Biol Chem 277:37029-36. 2002
    ..TANK was previously shown to assist NF-kappa B activation in a complex with TANK-binding kinase 1 (TBK1) or IKK epsilon, two kinases distantly related to IKK alpha/beta, but the underlying mechanisms remained unknown...
  63. doi IFN-induced TPR protein IFIT3 potentiates antiviral signaling by bridging MAVS and TBK1
    Xin Yi Liu
    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
    J Immunol 187:2559-68. 2011
    ..this leads to the activation of TNFR-associated factor family member-associated NF-κB activator-binding kinase 1 (TBK1) and phosphorylation of IFN regulatory factor 3 (IRF3). It remains to be elucidated how MAVS activates TBK1/IRF3...
  64. pmc ABIN1 protein cooperates with TAX1BP1 and A20 proteins to inhibit antiviral signaling
    Linlin Gao
    Department of Microbiology and Immunology, Graduate Program in Cancer Biology, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, Florida 33136, USA
    J Biol Chem 286:36592-602. 2011
    ..molecule TAX1BP1 and was essential for the recruitment of TAX1BP1 and A20 to the noncanonical IκB kinases TBK1 and IKKi in response to poly(I:C) transfection...
  65. pmc RING finger protein 11 targets TBK1/IKKi kinases to inhibit antiviral signaling
    Soratree Charoenthongtrakul
    Department of Microbiology and Immunology, The University of Miami, Miller School of Medicine, Miami, Florida, United States of America
    PLoS ONE 8:e53717. 2013
    ..RNF11 interacted with the noncanonical IKK kinases TBK1/IKKi and attenuated their Lys63-linked polyubiquitination by blocking interactions with the E3 ligase TRAF3...
  66. pmc Optineurin negatively regulates the induction of IFNbeta in response to RNA virus infection
    Jamel Mankouri
    Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom
    PLoS Pathog 6:e1000778. 2010
    ..and immunofluorescence studies identified optineurin in a protein complex containing the antiviral protein kinase TBK1 and the ubiquitin ligase TRAF3...
  67. pmc The leader proteinase of foot-and-mouth disease virus negatively regulates the type I interferon pathway by acting as a viral deubiquitinase
    Dang Wang
    Laboratory of Infectious Diseases, College of Veterinary Medicine, Huazhong Agricultural University, 1 Shi zi shan Street, Wuhan 430070, China
    J Virol 85:3758-66. 2011
    ..Lb(pro) significantly inhibited ubiquitination of retinoic acid-inducible gene I (RIG-I), TANK-binding kinase 1 (TBK1), TNF receptor-associated factor 6 (TRAF6), and TRAF3, key signaling molecules in activation of type I IFN response...
  68. ncbi Mutations in the chloride channel gene CLCNKB as a cause of classic Bartter syndrome
    M Konrad
    Department of Pediatrics, Philipps University, Marburg, Germany
    J Am Soc Nephrol 11:1449-59. 2000
    ..of the distal tubule, while HPS/aBS is caused by mutations in the gene for either the furosemide-sensitive NaK-2Cl-cotransporter NKCC2 (SLC12A1) or the inwardly rectifying potassium channel ROMK (KCNJ1)...
  69. doi Increased aerobic glycolysis through beta2 stimulation is a common mechanism involved in lactate formation during shock states
    Bruno Levy
    Groupe CHOC, Contrat AVENIR INSERM 2006, Faculte de Medecine, Nancy Universite, Vandoeuvre les Nancy, France
    Shock 30:417-21. 2008
    During septic shock, muscle produces lactate by way of an exaggerated NaK-adenosine triphosphatase (ATPase)-stimulated aerobic glycolysis associated with epinephrine stimulation possibly through beta2 adrenoreceptor involvement...
  70. pmc Infectivity enhancement by human immunodeficiency virus type 1 Nef is independent of its association with a cellular serine/threonine kinase
    T Luo
    Department of Virology and Molecular Biology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    J Virol 71:9524-30. 1997
    ..virus isolate mac239 (SIVmac239) have been found to associate with a cellular serine/threonine kinase designated NAK. We have recently shown that the association of Nef with NAK is isolate dependent...
  71. ncbi The NF-kappaB pathway in human endometrium and first trimester decidua
    A E King
    MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh, EH3 9ET, UK
    Mol Hum Reprod 7:175-83. 2001
    ..inducing kinase (NIK), mitogen-activated protein kinase Erk kinase kinase 1 (MEKK1) and TANK-binding kinase 1 (TBK1) using real-time quantitative polymerase chain reaction (PCR)...
  72. ncbi Value of transthoracic echocardiography in therapy regimens evaluation in pulmonary embolism
    Ling Zhu
    Department of Respiratory Medicine, Shandong Provincial Hospital, Shandong University, Jinan, China
    J Thromb Thrombolysis 26:251-6. 2008
    ..In this study, we assessed the changes of right ventricular (RV) function on transthoracic echocardiography (TTE) after different therapy strategies among a broad spectrum of APE...
  73. ncbi A mathematical model of the pancreatic duct cell generating high bicarbonate concentrations in pancreatic juice
    David C Whitcomb
    Department of Medicine, University of Pittsburgh, UPMC Presbyterian, Pittsburgh, Pennsylvania 15213, USA
    Pancreas 29:e30-40. 2004
    ..To develop a simple, physiologically based mathematical model of pancreatic duct cell secretion using experimentally derived parameters that generates pancreatic fluid bicarbonate concentrations of >140 mM after CFTR activation...
  74. doi Expression profiles of carp IRF-3/-7 correlate with the up-regulation of RIG-I/MAVS/TRAF3/TBK1, four pivotal molecules in RIG-I signaling pathway
    Hong Feng
    State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
    Fish Shellfish Immunol 30:1159-69. 2011
    ..signaling molecules, MAVS (mitochondrial antiviral signaling protein), TRAF3 (TNF-receptor-associated factor 3) and TBK1 (TANK-binding kinase 1), have significant roles in the recognition of cytoplasmic 5'-triphosphate ssRNA and short ..
  75. ncbi Postnatal maturation of the dog stria vascularis-- an immunohistochemical study
    Angélique G Coppens
    Laboratory of Anatomy and Embryology, Veterinary Anatomy, Free University of Brussels, Brussels, Belgium
    Anat Rec A Discov Mol Cell Evol Biol 270:82-92. 2003
    The lateral wall of the dog cochlear duct was investigated by classical staining and immunohistochemistry for NaK/ATPase beta2 isoform, cytokeratins (Cks), vimentin, nestin, and S100A6 during the postnatal cochlear maturation, i.e...
  76. ncbi Ion transport and barrier function in a telomerase-immortalized human nondysplastic, Barrett's cell line (BAR-T)
    Biljana Jovov
    Department of Medicine Gastroenterology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
    Dis Esophagus 22:386-95. 2009
    ..Membrane polarization was also documented in BAR-T by immunolocalization of NaK,ATPase to the basolateral membrane...
  77. pmc Severe acute respiratory syndrome coronavirus M protein inhibits type I interferon production by impeding the formation of TRAF3.TANK.TBK1/IKKepsilon complex
    Kam Leung Siu
    Department of Biochemistry, The University of Hong Kong, Pokfulam, Hong Kong
    J Biol Chem 284:16202-9. 2009
    ..activation of interferon-stimulated response element-dependent transcription by double-stranded RNA, RIG-I, MDA5, TBK1, IKKepsilon, and virus-induced signaling adaptor (VISA) but has no influence on the transcriptional activity of ..
  78. doi The T-helper cell type 1 immune response to gram-negative bacterial infections is impaired in COPD
    Jürgen Knobloch
    Department of Pneumology, Clinic III for Internal Medicine, University of Cologne, Kerpener Str 62, D 50937 Cologne, Germany
    Am J Respir Crit Care Med 183:204-14. 2011
    ..Toll-like receptor-4 (TLR4) detects bacteria via LPS and induces IFN-γ-based immune responses. The direct responsiveness of Th1 lymphocytes to LPS is disputed because they lack surface expression of the TLR4 coreceptor CD14...
  79. ncbi A novel thiocationic liposomal formulation of antisense oligonucleotides with activity against Mycobacterium tuberculosis
    Aditya R Das
    Inhale Therapeutic Systems, San Carlos, California 94070, USA
    Scand J Infect Dis 35:168-74. 2003
    ..These included the superoxide dismutase sod A gene (TBS3), catalase-peroxidase katG gene (TBK1, TBK10), RNA polymerase beta-subunit rpo B gene (TBR5) and diaminopimelate decarboxylase lys A gene (TBL5)...
  80. ncbi Toll-like receptor-dependent and -independent viperin gene expression and counter-regulation by PRDI-binding factor-1/BLIMP1
    Martina Severa
    Division of Infectious Disease and Immunology, Department of Medicine, The University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    J Biol Chem 281:26188-95. 2006
    ..LPS and poly(I-C) induce very high levels of Viperin in wild type cells but not in cells deficient in TRIF, TBK1, IRF3, or the type I IFNalpha/betaR...
  81. ncbi Bovine parainfluenza virus type 3 accessory proteins that suppress beta interferon production
    Takayuki Komatsu
    Microbiology Section, Department of Pathological Sciences, Faculty of Medical Sciences, University of Fukui, 23 3 Shimoaizuki, Matsuoka, Yoshida gun, Fukui 910 1193, Japan
    Microbes Infect 9:954-62. 2007
    ..enhanced by overexpression of MDA5 but not RIG-I, and yet does not suppress IFN-beta production induced by TRIF, TBK1, and IKKi. The V protein of both viruses specifically binds to MDA5 but not RIG-I...
  82. pmc Select paramyxoviral V proteins inhibit IRF3 activation by acting as alternative substrates for inhibitor of kappaB kinase epsilon (IKKe)/TBK1
    Lenette L Lu
    Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    J Biol Chem 283:14269-76. 2008
    ..between V and the IRF3/7 kinases, TRAF family member-associated NFkappaB activator (TANK)-binding kinase 1 (TBK1)/inhibitor of kappaB kinase epsilon (IKKe), was essential for this inhibition...
  83. pmc IRF7 activation by Epstein-Barr virus latent membrane protein 1 requires localization at activation sites and TRAF6, but not TRAF2 or TRAF3
    Yoon Jae Song
    Department of Microbiology, Channing Laboratory Brigham and Women s Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:18448-53. 2008
    ..IRF7 bound to LMP1, blocked IRF7 association and activation, but did not inhibit LMP1 induced NF-kappaB or TBK1 or Sendai virus-mediated IFN stimulated response element activation; and (ii) two different LMP1 transmembrane ..
  84. doi Determinants of K+ vs Na+ selectivity in potassium channels
    Todor Dudev
    Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
    J Am Chem Soc 131:8092-101. 2009
    ..herein help to rationalize why valinomycin and the KcsA ion channels are highly K(+)-selective, whereas the NaK channel is nonselective...
  85. pmc The C-terminal 42 residues of the Tula virus Gn protein regulate interferon induction
    Valery Matthys
    Department of Molecular Genetics and Microbiology, Stony Brook University, Life Sciences Room 126, Stony Brook, NY 11794 5222, USA
    J Virol 85:4752-60. 2011
    ..to results with pathogenic hantaviruses, expressing the TULV Gn protein cytoplasmic tail (Gn-T) blocked RIG-I- and TBK1-directed transcription from IFN-stimulated response elements (ISREs) and IFN-β promoters (>90%) but not ..
  86. ncbi Effect of thyroxine on cellular oxygen-consumption and glucose uptake: evidence of an effect of total T4 and not "free T4"
    J Kvetny
    Department of Clinical Chemistry and Internal Medicine C, Odense University Hospital, Denmark
    Horm Metab Res 22:485-9. 1990
    ..Inhibition of the NaK-ATPase by addition of ouabain (9-72 mg/l) did not inhibit T4 stimulation, thus indicating that the ouabain ..
  87. ncbi Occurrence of NaK-ATPase isoforms during rat inner ear development and functional implications
    T A Peters
    Department Otorhinolaryngology, University Medical Center St Radboud, Philips van Leydenlaan 15, 6500 HB Nijmegen, The Netherlands
    Eur Arch Otorhinolaryngol 258:67-73. 2001
    This study examined the presence of NaK-ATPase isoforms in the developing inner ear of the rat and studied the importance of functional subunit combinations in endolymph homeostasis...
  88. ncbi Two sibling cases of hydrops fetalis due to alloimmune anti-CD36 (Nak a) antibody
    Satoru Okajima
    Maternity and Perinatal Care Center, Hokkaido University Hospital, Hokkaido University School of Medicine, Kita 14 jo Nishi 5 chome, Kita ku, Sapporo 060 8648, Hokkaido, Japan
    Thromb Haemost 95:267-71. 2006
    ..The alloimmune anti-CD36 (Nak(a)) antibody was accidentally found in the mother's serum after an episode of anaphylactic shock with ..
  89. ncbi Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6
    Hans Hacker
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
    Nature 439:204-7. 2006
    ..Toll/IL-1 receptor domain-containing adaptor-inducing IFN-beta) and is required for marshalling the protein kinase TBK1 (also called NAK) into TIR signalling complexes, thereby explaining its unique role in activation of the IFN ..
  90. ncbi Regulation and function of IKK and IKK-related kinases
    Hans Hacker
    Department of Infectious Diseases, St Jude Children s Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA
    Sci STKE 2006:re13. 2006
    ..Several years ago, two protein kinases, one called IKKepsilon or IKK-i and one variously named TBK1 (TANK-binding kinase), NAK (NF-kappaB-activated kinase), or T2K (TRAF2-associated kinase), were identified that ..
  91. ncbi Regulation of interferon production by RIG-I and LGP2: a lesson in self-control
    Damien Vitour
    Hepacivirus Unit, Pasteur Institute, Paris Cedex 15, France
    Sci STKE 2007:pe20. 2007
    ..IPS-1, in turn, triggers signaling pathways, including activation of the protein kinases TBK1 and IKKepsilon, responsible for the phosphorylation of IRF3, a key transcription factor involved in interferon (IFN)..
  92. pmc Genetic dissection of interferon-antagonistic functions of rabies virus phosphoprotein: inhibition of interferon regulatory factor 3 activation is important for pathogenicity
    Martina Rieder
    Max von Pettenkofer Institute and Gene Center, Ludwig Maximilians University, D 81377 Munchen, Germany
    J Virol 85:842-52. 2011
    ..to 181, 182 to 186, or 176 to 186 were severely compromised in counteracting phosphorylation of IRF3 and IRF7 by TBK1 or IKKi while retaining the full capacity of preventing nuclear import of activated STATs and of supporting virus ..
  93. pmc Type I interferon production induced by Streptococcus pyogenes-derived nucleic acids is required for host protection
    Nina Gratz
    Max F Perutz Laboratories, Department of Microbiology, Immunobiology and Genetics, University of Vienna, Vienna, Austria
    PLoS Pathog 7:e1001345. 2011
    ..Macrophages required IRF3, STING, TBK1 and partially MyD88, whereas in cDCs the IFN-beta production was fully dependent on IRF5 and MyD88...
  94. doi Pemphigus vulgaris and its active disease mouse model
    Masayuki Amagai
    Department of Dermatology, School of Medicine, Keio University, Tokyo, Japan
    Curr Dir Autoimmun 10:167-81. 2008
    ..Subsequently, AK and NAK series of anti-Dsg3 IgG monoclonal antibodies were developed from the PV model mice...
  95. ncbi [Classic treatment of chronic heart insufficiency. What if new?]
    M C Aumont
    Service de cardiologie A, Hopital Bichat, Paris
    Arch Mal Coeur Vaiss 88:599-602. 1995
    ..Digitalis has a positive inotropic effect (inhibition of NaK-dependent ATPase)...
  96. ncbi Hypoglycemic potential of Morus indica. L and Costus igneus. Nak.--a preliminary study
    Vishalakshi D Devi
    Department of Studies in Food Science and Nutrition, University of Mysore, Manasagangotri, Mysore 570 006, India
    Indian J Exp Biol 46:614-6. 2008
    ..The preliminary results suggest that both the plants possess potent hypoglycemic activity...
  97. ncbi Ginkgo biloba extract (EGb 761) protects Na,K-ATPase isoenzymes during cerebral ischemia
    Sandrine Pierr
    Laboratoire de Recherche Cardiologique, Universite de la Mediterranee, Faculte de Medecine, IFR Jean Roche, Marseille, France
    Cell Mol Biol (Noisy-le-grand) 48:671-9. 2002
    ..Previous experiments have shown that EGb 761 protects NaK-ATPase activity against one hour of cerebral ischemia...
  98. doi Suppression of the TRIF-dependent signaling pathway of Toll-like receptors by luteolin
    Jun Kyung Lee
    Department of Life Science, Gwangju Institute of Science and Technology, Gwangju, 500 712, Republic of Korea
    Biochem Pharmacol 77:1391-400. 2009
    ..Luteolin attenuated ligand-independent activation of IRF3 or NFkappaB induced by TLR4, TRIF, or TBK1, while it did not inhibit TLR oligomerization...
  99. doi Hydration valve controlled non-selective conduction of Na(+) and K(+) in the NaK channel
    Rong Shen
    Institute of Nano Science, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China
    Biochim Biophys Acta 1798:1474-9. 2010
    ..Unlike a K(+) channel having four equivalent K(+)-binding sites in its selectivity filter, a NaK channel has a vestibule in the middle part of its selectivity filter, and can conduct both Na(+) and K(+) ions...
  100. doi Cloning, expression analysis and promoter structure of TBK1 (TANK-binding kinase 1) in Atlantic cod (Gadus morhua L.)
    Heng Chi
    Laboratory of Pathology and Immunology of Aquatic Animals, LMMEC, Ocean University of China, 266003 Qingdao, PR China
    Fish Shellfish Immunol 30:1055-63. 2011
    b>TBK1, also termed NAK or T2K, is a ubiquitous member of the IκB kinase (IKK) family that is required for innate and adaptive immune responses. We have identified and characterized the full-length TBK1 cDNA in Atlantic cod...
  101. ncbi Collisional transfer of population and orientation in NaK
    C M Wolfe
    Department of Physics, Lehigh University, Bethlehem, Pennsylvania 18015, USA
    J Chem Phys 134:174301. 2011
    ..quantitative information on the transfer of population and orientation in rotationally inelastic collisions of the NaK molecules prepared in the 2(A)(1)Σ(+)(v' = 16, J' = 30) rovibrational level with argon and potassium perturbers...

Research Grants71

  1. Innate Immunity: Signal Transduction and Interferon Gene Regulation
    THOMAS P MANIATIS; Fiscal Year: 2010
    ..The non-canonical I?B kinases TBK1 and IKK? play key roles in mediating this response...
  2. Zhijian J Chen; Fiscal Year: 2015
    ..MAVS resides on the mitochondrial outer membrane and it activates cytosolic protein kinases including IKK and TBK1, which phosphorylate the transcription factors NF-?B and IRF3, respectively...
  3. ALBERT SIDNEY BALDWIN; Fiscal Year: 2014
    ..Additional new data indicate that variant forms of IKK, namely TBK1 and IKKe, nuclear in human lung tumor cells and that a dominant negative form of IKKe blocks NF-kB activation in ..
  4. Role of a novel IKK-related kinase in inflammation
    SUSAN ELAINE SWEENEY; Fiscal Year: 2010
    ..The IKK-related kinases, inducible IKK (IKKi) and TANK-binding kinase 1 (TBK1) were as originally identified as NF-kB activating kinases that phosphorylated IkB...
  5. Regulation of Type I Interferon Gene Expression in the Innate Immune Response
    Katherine A Fitzgerald; Fiscal Year: 2012
    ..TANK-binding kinase (TBK1) is a central signaling hub in nucleic acid sensing pathways...
  6. The Role of Ubiquitination on TBK1 Function
    Roosevelt Boursiquot; Fiscal Year: 2010
    ..Preliminary studies showed that TRAFS's downstream target, TBK1, undergo K63-linked and K-48 linked polyubiquitination...
  7. Shen Ying Zhang; Fiscal Year: 2016
    ..We recently discovered an AR form of TLR3 deficiency, as well as AD TRIF, TRAF3 and TBK1 defects (unpublished)...
  8. Andrei E Medvedev; Fiscal Year: 2014
    ..adapter protein Mal;(ii) suppressed LPS-induced signalosome assembly amongst TLR4, adapter protein TRIF and kinase TBK1;(iii) deficient activation of TBK1 and transcription factor IRF-3;and (iv) increased expression of negative ..
  9. Martin E Dorf; Fiscal Year: 2015
    ..of innate antiviral immune responses have been highly influenced by the discovery of the IKK-related kinase, TBK1. Substrates for TBK1 include the transcription factor interferon regulatory factor (IRF)-3, which controls ..
  10. Ha Linh Vu; Fiscal Year: 2016
    ..One protein that may prove to be important in this group is TANK-binding kinase 1 (TBK1), an atypical IkB kinase family member...
  11. Bacterial effector inhibition of type I interferon
    PHILIP ROSS HARDWIDGE; Fiscal Year: 2012
    ..degradation-associated ubiquitination of TBK1, a host protein kinase essential to activation of type I IFN responses...
  12. Relative Roles of HSP70 and HSP25 in the Modulation of Renal Injury
    Rajasree Sreedharan; Fiscal Year: 2010
    ..injury, b) their interactions with a panel of proteins involved in maintenance of cellular integrity and polarity (NaK ATPase, ankyrin, spectrin and actin) and c) the molecular processes by which HSP interactions with these integrity ..
  13. Katherine A Fitzgerald; Fiscal Year: 2016
    ..Additional work from our laboratories has also implicated the DEAD box helicase DEAD box protein 3x (DDX3x) in the TBK1/IRF3 signaling pathway important for both RNA and cytoplasmic DNA pathways (including for IFI16), but its role in ..
  14. Deepak Shukla; Fiscal Year: 2014
    ..will focus on the possibility that HSV-1 infection interferes with OPTN phosphorylation by TANK binding kinase-1 (TBK1), which in turn results in the inhibition of autophagy induction and interferon production, and viral replication ..
  15. David A Barbie; Fiscal Year: 2014
    ..Specifically, the non-canonical I:B kinase TBK1, which is required for survival downstream of KRAS, will be the focus of further mechanistic studies, small ..
  16. Alan R Saltiel; Fiscal Year: 2016
    ..components to produce release of the Glut4 vesicle, concentrating on the exocyst protein Exo84 and the kinase TBK1;and 3) determining whether the Ral GAP complex plays an important in vivo role in glucose homeostasis by evaluating ..
  17. Shao Cong Sun; Fiscal Year: 2016
    ..In particular, we have identified two novel signaling factors the deubiquitinase Otud7b and the protein kinase TBK1, with pivotal roles in the negative regulation of noncanonical NF-[unreadable]B signaling...
  18. Youxing Jiang; Fiscal Year: 2016
    ..One is the non-selective, Ca2+ permeable cyclic nucleotide-gated (CNG) channels, using NaK from Bacillus cereus and its CNG- mimicking chimeras as model systems;the other is K+ selective channels, using a K+..
  19. Matthew L Meyerson; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): This Program aims to develop three protein kinases, inhibitor-resistant EGFR, TBK1, and DDR2, as therapeutic targets in non-small cell lung cancer (NSCLC)...
  20. SHANNON MARIE REILLY; Fiscal Year: 2014
    ..by applicant): The role of non-canonical IKKs in metabolic disease We hypothesize that hepatic IKK-epsilon and TBK1 are important metabolic mediators affecting hepatic steatosis and systemic metabolic disease...
  21. DEBORAH LYNN GALSON; Fiscal Year: 2016
    ..via activation of the two kB kinase (IKK)-related kinases IKKe (also called IKK-/) and TANK-binding kinase 1 (TBK1) and increased levels of RIP1 and TRAF2...
  22. Alan R Saltiel; Fiscal Year: 2014
    ..We hypothesize that the noncanonical Ikb kinases IKKe and TBK1 are "counterinflammatory" kinases that keep inflammatory pathways in check while helping to support a positive ..
  23. Regulation of Type I Interferon Gene Expression in the Innate Immune Response
    Katherine A Fitzgerald; Fiscal Year: 2010
    ..TBK-1 and IKKE phosphorylate and activate IRF3. TBK1 and IKKe are required for TLR and RNA helicase signaling...
  24. Francis Valiyaveetil; Fiscal Year: 2016
    ..Aim 1) To develop a chemical synthesis of the voltage gated K+ channel KvAP, and the non-selective channel, NaK. The chemical synthesis protocols that we develop in this aim will be useful not only in investigating these ..
  25. EFFECT OF VITAMIN E ON HEPATOCYTE STRUCTURE AND FUNCTION
    Ronald Sokol; Fiscal Year: 1991
    ..Taurocholate uptake, NaK-ATPase pump activity, ouabain uptake, and degree of lipid peroxidation will be determined in hepatocytes isolated ..
  26. ANTHONY JOHN CAPOBIANCO; Fiscal Year: 2016
    ..The underlying hypothesis of this proposal is that NAK is a transcriptional co-activator implicated in tumorigenesis...
  27. Alan R Saltiel; Fiscal Year: 2016
    ..aspect of counter-inflammation, paying particular attention to the induction of the kinases IKK[unreadable] and TBK1. We will knock these out in tissue-specific manner to determine the primary sites at which these events occur ..
  28. CALCIUM INDEPENDENT PLA2 AND ISCHEMIC CELL INJURY
    Didier Portilla; Fiscal Year: 2000
    ..proximal tubule contributes to cell injury by the formation of toxic amphiphiles which cause profound inhibition of NaK-ATPase during ischemia. We have purified a novel 28 kDa CaIPLA 2 enzyme from rabbit kidney cortex...
  29. Michael A White; Fiscal Year: 2015
    ..Our specific aims are 1) mechanistic elaboration of TBK1 as an oncology target in oncogenic Ras associated cancers;2) capture of oncogenic Ras synthetic-lethal loci by ..
  30. DIGITALIS-RECEPTOR OF THE HEART
    CSABA HEGYVARY; Fiscal Year: 1980
    This project is an investigation of the physiologic regulation of the digitalis-receptor (large subunit of NaK-ATPase) in the heart...
  31. NAK, A POTENTIAL THERAPEUTIC TARGET FOR AIDS
    Arie Abo; Fiscal Year: 2000
    ..we and others have shown that Nef is associated with the host protein kinase known as Nef Associated kinase (NAK). Recruitment of NAK by Nef is an important step for HIV production...
  32. A novel cytosolic immunosurveillance pathway
    RUSSELL E contact VANCE; Fiscal Year: 2010
    ..We show that induction of innate immune signaling pathways by c-di-GMP requires the TBK1 kinase and its target, the IRF3 transcription factor...
  33. PHARMACOLOGIC BASIS OF SMOOTH MUSCLE HETEROGENEITY
    JULIUS ALLEN; Fiscal Year: 2001
    ..tissues and Na- independent pump activation by numerous agonists in VSM we have identified at least 2 ways the NaK pump in this tissue can be modulated; 1) ion level activation by intracellular Na+ and 2) protein level activation ..
  34. INTERACTION OF PALYTOXIN WITH NAK-ATPASE PROTEOLIPOSOMES
    ATSUNOBU YODA; Fiscal Year: 1993
    ..due to digitalis is thought to be caused by a rise in intracellular Na+ level resulting from inhibition of the NaK-pump...
  35. The Angiotensin II-Induced JAK/STAT Pathway in Diabetes.
    Mario Marrero; Fiscal Year: 2005
    ..of this proposal is to define the molecular mechanisms by which HG enhances the Ang II-induce activation of the NAK/STAT pathway in an effort to elucidate the processes of increased VSMC growth and proliferation that occur during ..
  36. CONTROL OF MEMBRANE ACTIVITY BY NEUROTRANSMITTERS
    MABEL HOKIN; Fiscal Year: 1990
    ..of export protein (digestive enzymes) in the pancreas acinar cell, and the synthesis of the plasma membrane enzyme, NaK-ATPase, in the avian salt gland cell. 5...
  37. ACUTE RENAL FAILURE--IMPACT OF FLUORINATED ANESTHETICS
    RICHARD ZAGER; Fiscal Year: 2001
    ..The role of 3 specific anesthetic effects on tubule homeostasis (mitochondrial injury, NaK-ATPase inhibition, PLA2/activation-depletion) as "triggers" for anesthetic cytoresistance will be tested; and 3: ..
  38. Digoxin Chiral Isolates as Improved Pharmaceuticals
    John Somberg; Fiscal Year: 2005
    ..Digoxin is believed to augment contractility by inhibition of NaK+ATP'ace as well as of AV node delay by this mechanism...
  39. VASCULAR METABOLISM IN DIABETES
    Neil Ruderman; Fiscal Year: 1992
    ..The ability to maintain myo-inositol and glutathione content, NaK ATPase activity and AIB transport will be assessed in microvessels from at least two sites and in isolated ..
  40. LEUKEMOGENESIS BY ABL AND OTHER ONCOGENES
    David Baltimore; Fiscal Year: 2004
    ..4. NF-kappaB activation by TANK and TBK1. There are numerous pathways of NF-kappaB activation but none are known in precise detail...
  41. LOCATION OF CATION BINDING SITES IN NA+/K+ ATPASE
    JOSE ARGUELLO; Fiscal Year: 1999
    The long term goal of the candidate's research is to define structure- function relationship of the NaK-ATPase...
  42. Etiology of NaK-ATPase g-Subunit-Induced Hypomagnesaemia
    Robert Mercer; Fiscal Year: 2004
    ..In addition, these results may identify essential renal pathways responsible for degrading or refolding non-native proteins or pathways that influence stress induced apoptosis. ..
  43. Role of TBK1 polyubiquitination in innate antiviral immunity
    Martin E Dorf; Fiscal Year: 2010
    Studies of innate immune responses have been highly influenced by the discovery of the IKKrelated kinases, TBK1 and IKKe...
  44. The A2a adenosine receptor modulates hyaluronan mediated lung inflammation
    MAUREEN RENEE HORTON; Fiscal Year: 2010
    ..We believe that these studies will provide the pre-clinical basis for the use of A2aR specific agonists in the treatment of inflammatory lung diseases such as idiopathic pulmonary fibrosis, chronic bronchitis and emphysema. ..
  45. MECHANISM OF TRANSCRIPTIONAL INHIBITION BY IKB PROTEINS
    Gourisankar Ghosh; Fiscal Year: 2002
    ..These experiments will allow us to propose a model for how different complex formation between Rel/NFkappaB and IkappaB ultimately dictates the fate of a specific cell type. ..
  46. REGULATION OF MATRIX-INDUCED GENES IN LUNG MACROPHAGES
    Maureen Horton; Fiscal Year: 2003
    ..These studies should allow the applicant to further enhance and develop her research skills and enable her to pursue the basic molecular mechanisms of pulmonary fibrosis that might lead to novel treatment approaches. ..
  47. BACTERIAL INDUCTION OF CYTOKINE EXPRESSION IN THE LUNG
    Alice Prince; Fiscal Year: 2005
    ....
  48. NF-kappa beta in mRNA Stability and Cell Differentiation
    ALBERT BALDWIN JR; Fiscal Year: 2003
    ..abstract_text> ..
  49. CONTROL OF TNF SIGNALING BY NFKB
    ALBERT BALDWIN JR; Fiscal Year: 2003
    ..These experiments will provide new insight into mechanisms whereby TNFalpha initiates and controls critical pathways involved in mediating inflammatory, proliferative and apoptotic functions. ..
  50. MOLECULAR GENETICS OF HEREDITARY PANCREATITIS
    David Whitcomb; Fiscal Year: 2008
    ..The HP and familial pancreatitis studies are especially important because of the statistical power of family studies and the ability to detect modifier genes in a uniform background of susceptibility factors. ..
  51. NAPS2 Continuation - Genome-Wide Association Study of Pancreatitis
    David C Whitcomb; Fiscal Year: 2010
    ..Knowledge of the genetic basis of pancreatitis will lead to new treatments, and help remove the stigma that chronic pancreatitis is only a disease of drunkards. ..
  52. CF EPITHELIAL CELLS: INTERACTIONS WITH PSEUDOMONAS
    Alice Prince; Fiscal Year: 2005
    ..Using genetically defined mutants, the contribution of PLC to epithelial damage in normal and CF cells will be examined. ..
  53. International Consortium to Identify Genes and Interactions Controlling Oral Clef
    Terri Beaty; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  54. Influenza PDZ Ligand Directed Pathogenesis
    ERICH MACKOW; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  55. Combined Methods for Protein-Structure Prediction
    Kevin Karplus; Fiscal Year: 2007
    ....
  56. REGULATION OF BCL2 BY RAS AND TUMOR SUPPRESSORS
    ALBERT BALDWIN JR; Fiscal Year: 2001
    ....
  57. ROTAVIRUS VP5 PERMEABILIZES MEMBRANES
    ERICH MACKOW; Fiscal Year: 2002
    ..These studies address an essential step in the rotavirus entry process and basic mechanisms by which non-enveloped viral proteins permeabilize cellular membranes during entry. ..
  58. Antitumor Mechanisms of SRC Inhibitors in Lung Cancer
    Eric Haura; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  59. HANTAVIRUS CELL INTERACTIONS
    ERICH MACKOW; Fiscal Year: 2003
    ..Specific Aims: 1) beta3 Integrin Requirements for Hantavirus Infectivity; 2) Blocking beta3 Integrin-Hantavirus Interactions; 3) Transgenic Model of Hantavirus Infection and Pathogenesis. ..
  60. Intracellular Signaling Triggered by Tall-1/BCMA
    Hong Bing Shu; Fiscal Year: 2005
    ..The genes and their protein products identified in this study may be used as molecular targets for drug development against certain immune-deficient and autoimmune diseases. ..
  61. 14th Internatinal Symposium on Inherited Diseases
    David Whitcomb; Fiscal Year: 2004
    ..The format, venue, and content are designed to maximize participation, education, translation and implementation of the key elements of the many new findings in the genetics of the pancreas. ..
  62. High Performance Computer System for Molecular Modeling
    Benoit Roux; Fiscal Year: 2004
    ....
  63. NF-kappaB Regulation by Androgen Receptor
    ALBERT BALDWIN JR; Fiscal Year: 2004
    ..The experiments have the potential to identify a new target in the regulatory cascade associated with androgen/AR signaling and to possibly identify a new target for treatment of androgen-independent cancer. ..