IKKbeta

Summary

Gene Symbol: IKKbeta
Description: inhibitor of nuclear factor kappa B kinase subunit beta
Alias: IKK-beta, IKK2, IKKB, IMD15, NFKBIKB, inhibitor of nuclear factor kappa-B kinase subunit beta, I-kappa-B kinase 2, I-kappa-B-kinase beta, IKK-B, inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta, nuclear factor NF-kappa-B inhibitor kinase beta
Species: human

Top Publications

  1. doi IkappaB kinase beta (IKKbeta/IKK2/IKBKB)--a key molecule in signaling to the transcription factor NF-kappaB
    Johannes A Schmid
    Center for Biomolecular Medicine and Pharmacology, Medical University Vienna, Austria
    Cytokine Growth Factor Rev 19:157-65. 2008
  2. ncbi The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307)
    V Aguirre
    Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 275:9047-54. 2000
  3. ncbi Serine phosphorylation of insulin receptor substrate 1 by inhibitor kappa B kinase complex
    Zhanguo Gao
    Pennington Biomedical Research Center, Louisiana State University, Baton Rouge 70808, USA
    J Biol Chem 277:48115-21. 2002
  4. ncbi Caveolin-1 triggers T-cell activation via CD26 in association with CARMA1
    Kei Ohnuma
    Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4 6 1, Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    J Biol Chem 282:10117-31. 2007
  5. ncbi Mixed lineage kinase LZK and antioxidant protein-1 activate NF-kappaB synergistically
    Megumi Masaki
    Department of Biological Chemistry and CREST Core Research for Educational Science and Technology Project, Japan Science and Technology Corporation, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan
    Eur J Biochem 270:76-83. 2003
  6. pmc S6K directly phosphorylates IRS-1 on Ser-270 to promote insulin resistance in response to TNF-(alpha) signaling through IKK2
    Jin Zhang
    Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana 70808, USA
    J Biol Chem 283:35375-82. 2008
  7. pmc Interleukin-1 (IL-1) induces the Lys63-linked polyubiquitination of IL-1 receptor-associated kinase 1 to facilitate NEMO binding and the activation of IkappaBalpha kinase
    Mark Windheim
    MRC Protein Phosphorylation Unit, College of Life Sciences, The Sir James Black Centre, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, United Kingdom
    Mol Cell Biol 28:1783-91. 2008
  8. pmc IKK and NF-kappaB-mediated regulation of Claspin impacts on ATR checkpoint function
    Niall Steven Kenneth
    Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee, Scotland, UK
    EMBO J 29:2966-78. 2010
  9. ncbi 3-Phosphoinositide-dependent protein kinase-1-mediated IkappaB kinase beta (IkkB) phosphorylation activates NF-kappaB signaling
    Hiroshi Tanaka
    Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113 0032, Japan
    J Biol Chem 280:40965-73. 2005
  10. ncbi NF-kappaB activation upon interaction of HIV-1 envelope glycoproteins with cell surface CD4 involves IkappaB kinases
    Guillaume Bossis
    Laboratoire Infections Retrovirales et Signalisation Cellulaire, CNRS UMR 5121, Institut de Biologie, 4 Bd Henri IV, 34060, Montpellier, France
    FEBS Lett 516:257-64. 2002

Research Grants

  1. MATTHEW PETER COGGINS; Fiscal Year: 2014
  2. INDER MOHAN VERMA; Fiscal Year: 2014
  3. Negative regulation of NF-kB and inflammation by TAX1BP1
    Edward W Harhaj; Fiscal Year: 2012
  4. Biochemical Characterization of Yersinia Effector YopJ
    Kim Orth; Fiscal Year: 2012
  5. W Timothy Garvey; Fiscal Year: 2016
  6. Dongsheng Cai; Fiscal Year: 2016
  7. Dongsheng Cai; Fiscal Year: 2016
  8. Jianping Ye; Fiscal Year: 2015
  9. ALBERT SIDNEY BALDWIN; Fiscal Year: 2014
  10. Structural and functional studies of the IkappaB kinase (IKK) complex
    Hao Wu; Fiscal Year: 2013

Detail Information

Publications243 found, 100 shown here

  1. doi IkappaB kinase beta (IKKbeta/IKK2/IKBKB)--a key molecule in signaling to the transcription factor NF-kappaB
    Johannes A Schmid
    Center for Biomolecular Medicine and Pharmacology, Medical University Vienna, Austria
    Cytokine Growth Factor Rev 19:157-65. 2008
    b>IKKbeta/IKBKB (IkappaB kinase beta), also designated as IKK2, was named after its function of phosphorylating IkappaB molecules, the inhibitors of NF-kappaB transcription factors...
  2. ncbi The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307)
    V Aguirre
    Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 275:9047-54. 2000
    ..These results suggest that phosphorylation of serine 307 might mediate, at least partially, the inhibitory effect of proinflammatory cytokines like TNFalpha on IRS-1 function...
  3. ncbi Serine phosphorylation of insulin receptor substrate 1 by inhibitor kappa B kinase complex
    Zhanguo Gao
    Pennington Biomedical Research Center, Louisiana State University, Baton Rouge 70808, USA
    J Biol Chem 277:48115-21. 2002
    ....
  4. ncbi Caveolin-1 triggers T-cell activation via CD26 in association with CARMA1
    Kei Ohnuma
    Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4 6 1, Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    J Biol Chem 282:10117-31. 2007
    ..Taken together, our findings provide novel insights into the regulation of T-cell costimulation via the CD26 molecule...
  5. ncbi Mixed lineage kinase LZK and antioxidant protein-1 activate NF-kappaB synergistically
    Megumi Masaki
    Department of Biological Chemistry and CREST Core Research for Educational Science and Technology Project, Japan Science and Technology Corporation, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan
    Eur J Biochem 270:76-83. 2003
    ..We also provided evidence that LZK was associated directly with the IKK complex through the kinase domain, and that AOP-1 was recruited to the IKK complex through the binding to LZK...
  6. pmc S6K directly phosphorylates IRS-1 on Ser-270 to promote insulin resistance in response to TNF-(alpha) signaling through IKK2
    Jin Zhang
    Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana 70808, USA
    J Biol Chem 283:35375-82. 2008
    ..Moreover, in IKK2 (but not IKK1)-null cells, TNF-alpha treatment did not result in Thr-389 phosphorylation of S6K1...
  7. pmc Interleukin-1 (IL-1) induces the Lys63-linked polyubiquitination of IL-1 receptor-associated kinase 1 to facilitate NEMO binding and the activation of IkappaBalpha kinase
    Mark Windheim
    MRC Protein Phosphorylation Unit, College of Life Sciences, The Sir James Black Centre, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, United Kingdom
    Mol Cell Biol 28:1783-91. 2008
    ..Our data suggest a model in which the recruitment of the NEMO-IKK complex to K63-pUb-IRAK1 and the recruitment of the TAK1 complex to TRAF6 facilitate the TAK1-catalyzed activation of IKK by the TRAF6-IRAK1 complex...
  8. pmc IKK and NF-kappaB-mediated regulation of Claspin impacts on ATR checkpoint function
    Niall Steven Kenneth
    Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee, Scotland, UK
    EMBO J 29:2966-78. 2010
    ..These results uncover a novel function for IKK and NF-kappaB modulating the DNA-damage checkpoint response, allowing the cell to integrate different signalling pathways with the DNA-damage response...
  9. ncbi 3-Phosphoinositide-dependent protein kinase-1-mediated IkappaB kinase beta (IkkB) phosphorylation activates NF-kappaB signaling
    Hiroshi Tanaka
    Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113 0032, Japan
    J Biol Chem 280:40965-73. 2005
    ..We found that PDK1 directly phosphorylates IKKbeta at the Ser(181) residue in the activation loop, leading to NF-kappaB nuclear translocation and NF-kappaB-..
  10. ncbi NF-kappaB activation upon interaction of HIV-1 envelope glycoproteins with cell surface CD4 involves IkappaB kinases
    Guillaume Bossis
    Laboratoire Infections Retrovirales et Signalisation Cellulaire, CNRS UMR 5121, Institut de Biologie, 4 Bd Henri IV, 34060, Montpellier, France
    FEBS Lett 516:257-64. 2002
    ..Taken together, these results confirm that IKKs complex play a key role in gp120(env)-induced NF-kappaB activation...
  11. pmc Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) Coactivator activity by I kappa B kinase
    Ray Chang Wu
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Mol Cell Biol 22:3549-61. 2002
    ..Taken together, our results not only reveal the IKK-mediated phosphorylation of SRC-3 to be a regulated event that plays an important role but also substantiate the role of SRC-3 in multiple signaling pathways...
  12. 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
    ..Thus IKKε/TBK1 mediate the activation of Pellino 1's E3 ligase activity, as well as inducing the transcription of its gene and protein expression in response to TLR3 and TLR4 agonists...
  13. pmc Endotoxin tolerance impairs IL-1 receptor-associated kinase (IRAK) 4 and TGF-beta-activated kinase 1 activation, K63-linked polyubiquitination and assembly of IRAK1, TNF receptor-associated factor 6, and IkappaB kinase gamma and increases A20 expression
    Yanbao Xiong
    Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
    J Biol Chem 286:7905-16. 2011
    ....
  14. pmc A herpesvirus virulence factor inhibits dendritic cell maturation through protein phosphatase 1 and Ikappa B kinase
    Huali Jin
    Department of Microbiology and Immunology M C 790, College of Medicine, University of Illinois, Chicago, 835 South Wolcott Avenue, Chicago, IL 60612, USA
    J Virol 85:3397-407. 2011
    ..Deletions or mutations in either domain abolish the activity of γ(1)34.5. These results suggest that the control of IκB kinase dephosphorylation by γ(1)34.5 represents a critical viral mechanism to disrupt dendritic cell functions...
  15. ncbi Decoy receptor 3 expression in AsPC-1 human pancreatic adenocarcinoma cells via the phosphatidylinositol 3-kinase-, Akt-, and NF-kappa B-dependent pathway
    Pei Hsuan Chen
    School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan
    J Immunol 181:8441-9. 2008
    ....
  16. ncbi Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action
    Vincent Aguirre
    Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 277:1531-7. 2002
    ..These results suggest that inhibition of PTB domain function in IRS-1 by phosphorylation of Ser(307) (Ser(312) in human IRS-1) might be a general mechanism to regulate insulin signaling...
  17. 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...
  18. pmc Molecular mechanism of hTid-1, the human homolog of Drosophila tumor suppressor l(2)Tid, in the regulation of NF-kappaB activity and suppression of tumor growth
    Hua Cheng
    Department of Cancer Biology, University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Mol Cell Biol 25:44-59. 2005
    ..Collectively, the data suggest that hTid-1 represses the activity of NF-kappaB through physical and functional interactions with the IKK complex and IkappaB and, in doing so, it modulates cell growth and death...
  19. ncbi Functional role of c-Src in IL-1-induced NF-kappa B activation: c-Src is a component of the IKK complex
    Megumi Funakoshi-Tago
    Department of Biochemistry and Immunology, Kyoritsu University of Pharmacy, 1 5 30 Shibakoen, Minato ku, Tokyo 105 8512
    J Biochem 137:189-97. 2005
    ..Taken together, our results suggest that c-Src plays a critical role in IL-1-induced NF-kappa B activation through the IKK complex...
  20. pmc Regulation of I(kappa)B kinase complex by phosphorylation of (gamma)-binding domain of I(kappa)B kinase (beta) by Polo-like kinase 1
    Tomoyasu Higashimoto
    Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA 90089 9176, USA
    J Biol Chem 283:35354-67. 2008
    ..interaction of the IKKgamma (NEMO) subunit with the C-terminal IKKgamma/NEMO-binding domain (gammaBD) of IKKbeta is an essential interaction for IKK regulation...
  21. doi Akt/Nox2/NF-κB signaling pathway is involved in Tat-induced HIV-1 long terminal repeat (LTR) transactivation
    Hong Sheng Zhang
    Beijing University of Technology, District of Chaoyang, China
    Arch Biochem Biophys 505:266-72. 2011
    ....
  22. ncbi The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation
    E Zandi
    Department of Pharmacology, University of California at San Diego, La Jolla 92093 0636, USA
    Cell 91:243-52. 1997
    ..We now describe the molecular cloning and characterization of IKKbeta, a second subunit of the IKK complex...
  23. ncbi Tumor necrosis factor receptor-associated factors (TRAFs)--a family of adapter proteins that regulates life and death
    R H Arch
    Gwen Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, Illinois 60637 USA
    Genes Dev 12:2821-30. 1998
  24. pmc The alpha and beta subunits of IkappaB kinase (IKK) mediate TRAF2-dependent IKK recruitment to tumor necrosis factor (TNF) receptor 1 in response to TNF
    A Devin
    Department of Cell and Cancer Biology, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Mol Cell Biol 21:3986-94. 2001
    ..IKK is a complex composed of three subunits: IKKalpha, IKKbeta, and IKKgamma (also called NEMO)...
  25. ncbi Tumor necrosis factor receptor-associated factor 1 gene overexpression in B-cell chronic lymphocytic leukemia: analysis of NF-kappa B/Rel-regulated inhibitors of apoptosis
    Gerd Munzert
    Abteilung Innere Medizin III and Abteilung Innere Medizin I, Universitat Ulm, Ulm, Germany
    Blood 100:3749-56. 2002
    ..Thus, although our study revealed a common expression pattern of NF-kappaB/Rel-regulated inhibitors of apoptosis, our findings indicate an IKK-independent regulation of TRAF1 in B-CLL...
  26. ncbi PAN1/NALP2/PYPAF2, an inducible inflammatory mediator that regulates NF-kappaB and caspase-1 activation in macrophages
    Jean Marie Bruey
    Burnham Institute, La Jolla, California 92037, USA
    J Biol Chem 279:51897-907. 2004
    ..We propose that PAN1 functions as a modulator of the activation of NF-kappaB and pro-caspase-1 in macrophages...
  27. 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
    ..interference directed at IkappaB kinase (IKK)-alpha/beta (the best characterized Ser-536 kinases so far) or the IKKbeta inhibitor SC-514 or dominant negative mutants of either IKK...
  28. ncbi Common inhibitory serine sites phosphorylated by IRS-1 kinases, triggered by insulin and inducers of insulin resistance
    Avia Herschkovitz
    Department of Molecular Cell Biology, The Weizmann Institute of Science, Faculty of Agricultural, Food, and Environmental Quality, The Hebrew University of Jerusalem, Rehovot, Israel
    J Biol Chem 282:18018-27. 2007
    ..Here we show that in Fao rat hepatoma cells, the IkappaB kinase beta (IKKbeta) is an IRS-1 kinase activated by selected inducers of insulin resistance, including sphingomyelinase, ceramide, ..
  29. ncbi Activation of the Ikappa B kinases by RIP via IKKgamma /NEMO-mediated oligomerization
    J L Poyet
    Center for Apoptosis Research and the Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Biol Chem 275:37966-77. 2000
    ..Enforced oligomerization of the N terminus of IKKgamma or truncated IKKalpha or IKKbeta lacking their serine-cluster domains can also induce IKK and NF-kappaB activation...
  30. ncbi Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain
    L Deng
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas 75390, USA
    Cell 103:351-61. 2000
    ..These results unveil a new regulatory function for ubiquitin, in which IKK is activated through the assembly of K63-linked polyubiquitin chains...
  31. ncbi A resorcylic acid lactone, 5Z-7-oxozeaenol, prevents inflammation by inhibiting the catalytic activity of TAK1 MAPK kinase kinase
    Jun Ninomiya-Tsuji
    Department of Molecular Biology, Graduate School of Science, Nagoya University, and CREST, Japan Science and Technology Corporation, Chikusa ku, Nagoya 464 8602, Japan
    J Biol Chem 278:18485-90. 2003
    ..Furthermore, in vivo 5Z-7-oxozeaenol was able to inhibit picryl chloride-induced ear swelling. Thus, 5Z-7-oxozeaenol blocks proinflammatory signaling by selectively inhibiting TAK1 MAPKKK...
  32. pmc Dimerization of the I kappa B kinase-binding domain of NEMO is required for tumor necrosis factor alpha-induced NF-kappa B activity
    Ralf B Marienfeld
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University Medical School, New Haven, CT 06520, USA
    Mol Cell Biol 26:9209-19. 2006
    ..corresponding to a six-amino-acid NEMO-binding domain from the C terminus of IkappaB kinase alpha (IKKalpha) and IKKbeta can disrupt the IKK complex and block NF-kappaB activation...
  33. pmc Regulation of IKKbeta by miR-199a affects NF-kappaB activity in ovarian cancer cells
    R Chen
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA
    Oncogene 27:4712-23. 2008
    ..Cancer progression is an abnormal form of tissue repair characterized by chronic inflammation. IkappaB kinase-beta (IKKbeta) required for nuclear factor-kappaB (NF-kappaB) activation plays a critical role in this process...
  34. pmc Phosphorylation of p53 by IkappaB kinase 2 promotes its degradation by beta-TrCP
    Yifeng Xia
    Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 106:2629-34. 2009
    ..In this study, we show that IkappaB kinase 2 (IKK2/IKKbeta), which is critical for NF-kappaB activation, also phosphorylates p53...
  35. doi Recruitment of the linear ubiquitin chain assembly complex stabilizes the TNF-R1 signaling complex and is required for TNF-mediated gene induction
    Tobias L Haas
    Division of Apoptosis Regulation, German Cancer Research Center DKFZ, 69120 Heidelberg, Germany
    Mol Cell 36:831-44. 2009
    ..Finally, we demonstrate that sustained stability of the TNF-RSC requires LUBAC's enzymatic activity, thereby adding a third form of ubiquitin linkage to the triggering of TNF signaling by the TNF-RSC...
  36. doi HIV-1 Nef interacts with HCV Core, recruits TRAF2, TRAF5 and TRAF6, and stimulates HIV-1 replication in macrophages
    Kashif A Khan
    Department of Virology, UPRES EA4266 Pathogens and Inflammation, SFR FED 4234, University of Franche Comte, CHU Besancon, Besancon, France
    J Innate Immun 5:639-56. 2013
    ....
  37. ncbi Site-specific phosphorylation of IkappaBalpha by a novel ubiquitination-dependent protein kinase activity
    Z J Chen
    ProScript Incorporated, Cambridge, Massachusetts, 02139, USA
    Cell 84:853-62. 1996
    ..We also show that a ubiquitination event in the kinase complex is a prerequisite for specific phosphorylation of IkappaBalpha. Thus, ubiquitination serves a novel regulatory function that does not involve proteolysis...
  38. pmc Mapping of the inducible IkappaB phosphorylation sites that signal its ubiquitination and degradation
    J Didonato
    Department of Pharmacology, Program in Biomedical Science, University of California, San Diego School of Medicine, La Jolla, USA
    Mol Cell Biol 16:1295-304. 1996
    ..As substitution of a conserved lysine residue slows down the ubiquitination and degradation of IkappaBalpha without affecting its phosphorylation, polyubiquitination is required for inducible IkappaB degradation...
  39. ncbi A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB
    J A DiDonato
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California at San Diego, La Jolla 92093 0636, USA
    Nature 388:548-54. 1997
    ..A component of IKK was molecularly cloned and identified as a serine kinase. IKK turns out to be the long-sought-after protein kinase that mediates the critical regulatory step in NF-kappaB activation...
  40. ncbi IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF-kappaB activation
    F Mercurio
    Signal Pharmaceuticals, Inc, 5555 Oberlin Drive, San Diego, CA 92121, USA
    Science 278:860-6. 1997
    ..Mutant versions of IKK-2 had pronounced effects on RelA nuclear translocation and NF-kappaB-dependent reporter activity, consistent with a critical role for the IKK kinases in the NF-kappaB signaling pathway...
  41. ncbi IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK
    J D Woronicz
    Tularik, Two Corporate Drive, South San Francisco, CA 94080, USA
    Science 278:866-9. 1997
    ..Overexpression of a catalytically inactive form of IKK-beta blocked cytokine-induced NF-kappaB activation. Thus, an active IkappaB kinase complex may require three distinct protein kinases...
  42. pmc NF-kappaB-inducing kinase activates IKK-alpha by phosphorylation of Ser-176
    L Ling
    Tularik, Inc, Two Corporate Drive, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 95:3792-7. 1998
    ..Conversely, a mutant form of IKK-alpha containing glutamic acid at residue 176 is constitutively active. Thus, the phosphorylation of IKK-alpha on Ser-176 by NIK may be required for cytokine-mediated NF-kappaB activation...
  43. ncbi Direct phosphorylation of IkappaB by IKKalpha and IKKbeta: discrimination between free and NF-kappaB-bound substrate
    E Zandi
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Science 281:1360-3. 1998
    ..Two subunits of this complex, IkappaB kinase alpha (IKKalpha) and IkappaB kinase beta (IKKbeta), are required for NF-kappaB activation...
  44. ncbi IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex
    D M Rothwarf
    Department of Pharmacology, University of California San Diego, La Jolla 92093 0636, USA
    Nature 395:297-300. 1998
    ..IKK-gamma interacts preferentially with IKK-beta and is required for the activation of the IKK complex. An IKK-gamma carboxy-terminal truncation mutant that still binds IKK-beta blocks the activation of IKK and NF-kappaB...
  45. pmc Coordinate regulation of IkappaB kinases by mitogen-activated protein kinase kinase kinase 1 and NF-kappaB-inducing kinase
    S Nemoto
    Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
    Mol Cell Biol 18:7336-43. 1998
    IkappaB kinases (IKKalpha and IKKbeta) are key components of the IKK complex that mediates activation of the transcription factor NF-kappaB in response to extracellular stimuli such as inflammatory cytokines, viral and bacterial ..
  46. pmc IkappaB kinase (IKK)-associated protein 1, a common component of the heterogeneous IKK complex
    F Mercurio
    Signal Pharmaceuticals, Inc, San Diego, California 92121, USA
    Mol Cell Biol 19:1526-38. 1999
    ..multiprotein complex, the IkappaB kinase (IKK) signalsome, which contains two regulated IkappaB kinases, IKK1 and IKK2, that can each phosphorylate IkappaBalpha and IkappaBbeta...
  47. ncbi Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation
    M Delhase
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0636, USA
    Science 284:309-13. 1999
    ..IKK is composed of three subunits-IKKalpha and IKKbeta, which are highly similar protein kinases, and IKKgamma, a regulatory subunit...
  48. ncbi Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation
    S Q Zhang
    Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel
    Immunity 12:301-11. 2000
    ..as well as recruitment of RIP to the receptor together with the three major signalosome components, NEMO, IKK1 and IKK2, and some kind of covalent modification of the recruited RIP molecules...
  49. ncbi Role of IKKgamma/nemo in assembly of the Ikappa B kinase complex
    X H Li
    Division of Hematology Oncology, Department of Medicine, Harold Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390 8594
    J Biol Chem 276:4494-500. 2001
    ..When expressed alone following transfection, IKKalpha and IKKbeta were present in low molecular weight complexes migrating between 200 and 400 kDa...
  50. ncbi Direct phosphorylation of NF-kappaB1 p105 by the IkappaB kinase complex on serine 927 is essential for signal-induced p105 proteolysis
    A Salmeron
    Division of Cellular Immunology, The National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom
    J Biol Chem 276:22215-22. 2001
    ..individually changed to alanine established that only serine 927 is essential for p105 proteolysis triggered by IKK2 overexpression. This residue is also required for TNFalpha and IL-1alpha to stimulate p105 degradation...
  51. ncbi TAK1 is a ubiquitin-dependent kinase of MKK and IKK
    C Wang
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9148, USA
    Nature 412:346-51. 2001
    ..We also provide evidence that TRAF6 is conjugated by the K63 polyubiquitin chains. These results indicate that ubiquitination has an important regulatory role in stress response pathways, including those of IKK and JNK...
  52. ncbi Regulation of beta-catenin function by the IkappaB kinases
    C Lamberti
    Division of Hematology Oncology, Department of Medicine, Harold Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 276:42276-86. 2001
    ..Two kinases, IKKalpha and IKKbeta, are critical activators of the NF-kappaB pathway...
  53. ncbi The human herpes virus 8-encoded viral FLICE inhibitory protein physically associates with and persistently activates the Ikappa B kinase complex
    Li Liu
    Hamon Center for Therapeutic Oncology Research and Division of Hematology Oncology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 8593, USA
    J Biol Chem 277:13745-51. 2002
    ..gets recruited to a approximately 700-kDa IkappaB kinase (IKK) complex and physically associates with IKKalpha, IKKbeta, NEMO/IKKgamma, and RIP...
  54. ncbi TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90
    Guoqing Chen
    Tularik, Incorporated, Two Corporate Drive, South San Francisco, CA 94080, USA
    Mol Cell 9:401-10. 2002
    The IKK complex, containing two catalytic subunits IKKalpha and IKKbeta and a regulatory subunit NEMO, plays central roles in signal-dependent activation of NF-kappaB...
  55. ncbi Characterization of the Ikappa B-kinase NEMO binding domain
    Michael J May
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University Medical School, New Haven, Connecticut 06520, USA
    J Biol Chem 277:45992-6000. 2002
    ..requires an upstream kinase complex (IkappaB-kinase; IKK) composed of two catalytic subunits (IKKalpha and IKKbeta) and a noncatalytic regulatory component named NEMO (NF-kappaB essential modulator)...
  56. ncbi TAK1 is critical for IkappaB kinase-mediated activation of the NF-kappaB pathway
    Giichi Takaesu
    Division of Hematology Oncology, Department of Medicine, Harold Simmons Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 8594, USA
    J Mol Biol 326:105-15. 2003
    Cytokine treatment stimulates the IkappaB kinases, IKKalpha and IKKbeta, which phosphorylate the IkappaB proteins, leading to their degradation and activation of NF-kappaB regulated genes...
  57. pmc Tetrameric oligomerization of IkappaB kinase gamma (IKKgamma) is obligatory for IKK complex activity and NF-kappaB activation
    Sebastian Tegethoff
    Cell Growth and Differentiation Program, Max Delbruck Center for Molecular Medicine, Robert Rossle Strasse 10, 13092 Berlin, Germany
    Mol Cell Biol 23:2029-41. 2003
    ..Its catalytic subunits, IKKalpha and IKKbeta, require association with the regulatory IKKgamma (NEMO) component to gain full basal and inducible kinase ..
  58. ncbi GMCSF activates NF-kappaB via direct interaction of the GMCSF receptor with IkappaB kinase beta
    Karin Ebner
    Department of Vascular Biology and Thrombosis Research, University of Vienna, Brunnerstrasse 59, A 1235 Vienna, Austria
    Blood 102:192-9. 2003
    ..Fluorescence resonance energy transfer (FRET) microscopy confirmed the direct interaction of CFP-IKKbeta and YFPGMRalpha in living cells...
  59. ncbi c-Src-dependent tyrosine phosphorylation of IKKbeta is involved in tumor necrosis factor-alpha-induced intercellular adhesion molecule-1 expression
    Wei Chien Huang
    Department of Pharmacology, College of Medicine, National Taiwan University, Taipei 10018, Taiwan
    J Biol Chem 278:9944-52. 2003
    ..plasmids induced ICAM-1 promoter activity, this effect being inhibited by the dominant-negative c-Src (KM) or IKKbeta (KM) mutant but not by the nuclear factor-kappaB-inducing kinase (NIK) (KA) mutant...
  60. ncbi In vivo identification of inducible phosphoacceptors in the IKKgamma/NEMO subunit of human IkappaB kinase
    Robert S Carter
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0295, USA
    J Biol Chem 278:19642-8. 2003
    ..IKK contains two structurally related catalytic subunits termed IKKalpha and IKKbeta as well as a noncatalytic subunit called IKKgamma/NEMO...
  61. ncbi Caspase-mediated cleavage converts the tumor necrosis factor (TNF) receptor-associated factor (TRAF)-1 from a selective modulator of TNF receptor signaling to a general inhibitor of NF-kappaB activation
    Frank Henkler
    Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany
    J Biol Chem 278:29216-30. 2003
    ....
  62. ncbi Tumor necrosis factor-alpha-induced IKK phosphorylation of NF-kappaB p65 on serine 536 is mediated through the TRAF2, TRAF5, and TAK1 signaling pathway
    Hiroaki Sakurai
    Department of Pathogenic Biochemistry, Institute of Natural Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama 930 0194, Japan
    J Biol Chem 278:36916-23. 2003
    ..In addition, overexpression of TGF-beta-activated kinase 1 (TAK1), IKKalpha and IKKbeta stimulated the phosphorylation, and their dominant negative mutants blocked the TNF-alpha-induced phosphorylation...
  63. ncbi Bcl10 activates the NF-kappaB pathway through ubiquitination of NEMO
    Honglin Zhou
    Department of Molecular Oncology, Genentech Inc 1 DNA Way, South San Francisco, California 94080, USA
    Nature 427:167-71. 2004
    ..Thus, the adaptor protein Bcl10 promotes activation of NF-kappaB transcription factors through paracaspase- and UBC13-dependent ubiquitination of NEMO...
  64. ncbi IkappaB kinase promotes tumorigenesis through inhibition of forkhead FOXO3a
    Mickey C T Hu
    Department of Molecular and Cellular Oncology, The University of Texas, Houston, TX 77030, USA
    Cell 117:225-37. 2004
    ..Cytoplasmic FOXO3a correlates with expression of IKKbeta or Akt-p in many tumors and associates with poor survival in breast cancer...
  65. ncbi Evaluation of nuclear factor-kappaB, urokinase-type plasminogen activator, and HBx and their clinicopathological significance in hepatocellular carcinoma
    Chun Fung Chan
    Department of Pathology, Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
    Clin Cancer Res 10:4140-9. 2004
    ..The purpose of this study was to evaluate NF-kappaB activation, uPA up-regulation, and hepatitis B viral X protein (HBx) expression in human hepatocellular carcinoma (HCC) and to assess their clinicopathological significance...
  66. ncbi Activation of transcription factor NF-kappaB requires ELKS, an IkappaB kinase regulatory subunit
    Jeanette L Ducut Sigala
    Salk Institute for Biological Sciences, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 304:1963-7. 2004
    ..These cells were also not protected from apoptosis in response to cytokines. ELKS likely functions by recruiting IkappaBalpha to the IKK complex and thus serves a regulatory function for IKK activation...
  67. ncbi The C-terminal activating region 2 of the Epstein-Barr virus-encoded latent membrane protein 1 activates NF-kappaB through TRAF6 and TAK1
    Liming Wu
    Department of Biochemistry, Hong Kong University of Science and Technology, Clearwater Bay, Kowloon, Hong Kong, China
    J Biol Chem 281:2162-9. 2006
    ..Thus, LMP1 utilizes two distinct pathways to activate NF-kappaB: a major one through CTAR2/TRAF6/TAK1/IKKbeta (canonical pathway) and a minor one through CTAR1/TRAF3/NIK/IKKalpha (noncanonical pathway).
  68. ncbi Molecular linkage between the kinase ATM and NF-kappaB signaling in response to genotoxic stimuli
    Zhao Hui Wu
    Department of Pharmacology, University of Wisconsin Madison, 301 SMI, 1300 University Avenue, Madison, WI 53706, USA
    Science 311:1141-6. 2006
    ..Thus, regulated nuclear shuttling of NEMO links two signaling kinases, ATM and IKK, to activate NF-kappaB by genotoxic signals...
  69. ncbi Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-kappaB activation [corrected]
    Chuan Jin Wu
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Nat Cell Biol 8:398-406. 2006
    ..IKK has two catalytic subunits, IKKalpha and IKKbeta, and a regulatory subunit, IKKgamma or NEMO...
  70. ncbi NEMO binding domain of IKK-2 encompasses amino acids 735-745
    Joann Strnad
    Drug Discovery Research, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA
    J Mol Recognit 19:227-33. 2006
    ..These longer NBD-containing peptides may be required to give the NBD an appropriate conformation for recognition by NEMO and/or to provide for additional interactions with NEMO...
  71. ncbi Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO
    Chee Kwee Ea
    Howard Hughes Medical Institute, Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Mol Cell 22:245-57. 2006
    ..These results reveal the biochemical mechanism underlying the essential signaling function of NEMO and provide direct evidence that signal-induced site-specific ubiquitination of RIP1 is required for IKK activation...
  72. pmc An alternative splice product of IkappaB kinase (IKKgamma), IKKgamma-delta, differentially mediates cytokine and human T-cell leukemia virus type 1 tax-induced NF-kappaB activation
    Tao Hai
    Department of Internal Medicine, The University of Texas Medical Branch, 301 University Blvd, Galveston, Texas 77555 1060, USA
    J Virol 80:4227-41. 2006
    ..The core IKK consists of two catalytic serine kinases, IKKalpha and IKKbeta, and a noncatalytic subunit, IKKgamma...
  73. 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
    ..Two protein kinases with a high degree of sequence similarity, IKKalpha and IKKbeta, mediate phosphorylation of IkappaB proteins and represent a convergence point for most signal transduction ..
  74. pmc Prolyl hydroxylase-1 negatively regulates IkappaB kinase-beta, giving insight into hypoxia-induced NFkappaB activity
    Eoin P Cummins
    Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
    Proc Natl Acad Sci U S A 103:18154-9. 2006
    ..we demonstrate that hypoxia activates NFkappaB through a pathway involving activation of IkappaB kinase-beta (IKKbeta) leading to phosphorylation-dependent degradation of IkappaBalpha and liberation of NFkappaB...
  75. pmc In vitro treatment of human monocytes/macrophages with myristoylated recombinant Nef of human immunodeficiency virus type 1 leads to the activation of mitogen-activated protein kinases, IkappaB kinases, and interferon regulatory factor 3 and to the releas
    Giorgio Mangino
    Department of Biology University Roma Tre, Viale G Marconi 446, 00146 Rome, Italy
    J Virol 81:2777-91. 2007
    ..In addition, we have observed the activation of interferon regulatory factor 3, leading to the synthesis of beta interferon mRNA and protein, which in turn induces STAT2 phosphorylation. All of these effects require Nef myristoylation...
  76. pmc Interleukin-1-induced NF-kappaB activation is NEMO-dependent but does not require IKKbeta
    Laura A Solt
    Department of Animal Biology, University of Pennsylvania School of Veterinary Medicine, PA 19104, USA
    J Biol Chem 282:8724-33. 2007
    ..and interleukin-1 (IL-1) requires the IkappaB kinase (IKK) complex, which contains two kinases named IKKalpha and IKKbeta and a critical regulatory subunit named NEMO...
  77. pmc Retroviral oncoprotein Tax deregulates NF-kappaB by activating Tak1 and mediating the physical association of Tak1-IKK
    Xuefeng Wu
    Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey Medical Center, PO Box 850, Hershey, Pennsylvania 17033, USA
    EMBO Rep 8:510-5. 2007
    ..These findings show a pathological mechanism of IKK activation by Tax and provide an example for how IKK is persistently activated in cancer cells...
  78. ncbi IKK beta suppression of TSC1 links inflammation and tumor angiogenesis via the mTOR pathway
    Dung Fang Lee
    Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cell 130:440-55. 2007
    ..Here we show that IKKbeta, a major downstream kinase in the TNFalpha signaling pathway, physically interacts with and phosphorylates TSC1 ..
  79. ncbi Phosphorylation of serine 68 in the IkappaB kinase (IKK)-binding domain of NEMO interferes with the structure of the IKK complex and tumor necrosis factor-alpha-induced NF-kappaB activity
    Lysann Palkowitsch
    Institute of Physiological Chemistry, Ulm University, Albert Einstein Allee 11, Ulm 89081, Germany
    J Biol Chem 283:76-86. 2008
    ..Besides the two kinases IKKalpha and IKKbeta, the IKK complex contains NEMO/IKKgamma, an additional subunit with regulatory and adaptor functions...
  80. pmc High-affinity interaction between IKKbeta and NEMO
    Yu Chih Lo
    Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA
    Biochemistry 47:3109-16. 2008
    The Ser/Thr-specific IkappaB kinase (IKK), which comprises IKKalpha or IKKbeta and the regulatory protein NEMO, is at the bottleneck for NF-kappaB activation. IKK activity relies on interaction between NEMO and IKKalpha or IKKbeta...
  81. pmc Inhibition of IkappaB kinase by vaccinia virus virulence factor B14
    Ron A J Chen
    Department of Virology, Faculty of Medicine, Imperial College London, London, United Kingdom
    PLoS Pathog 4:e22. 2008
    ..Notably, the interaction between B14 and the IKK complex required IKKbeta but not IKKalpha, suggesting the interaction occurs via IKKbeta...
  82. pmc Akt-dependent regulation of NF-{kappa}B is controlled by mTOR and Raptor in association with IKK
    Han C Dan
    Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
    Genes Dev 22:1490-500. 2008
    ..The results provide insight into the effects of Akt/mTOR-dependent signaling on gene expression and into the therapeutic action of rapamycin...
  83. pmc The IkappaB kinase complex: master regulator of NF-kappaB signaling
    Laura A Solt
    Department of Animal Biology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street OVH 200E, Philadelphia, PA, 19104 6045, USA
    Immunol Res 42:3-18. 2008
    ..NF-kappaB signaling pathways is the IkappaB kinase (IKK) complex that consists of two kinases (IKKalpha and IKKbeta) and a regulatory subunit named NF-kappaB essential modulator (NEMO)...
  84. doi The human IKKbeta subunit kinase domain displays CK2-like phosphorylation specificity
    Jacob D Shaul
    Structural Biochemistry Laboratory, Department of Chemistry and Biochemistry, Mail Code 1030, 5500 Campanile Drive, San Diego State University, San Diego, CA 92182 1030, USA
    Biochem Biophys Res Commun 374:592-7. 2008
    ..In this study, we build upon the observation that highly purified human IKKbeta subunit preparations retain this specificity in vitro...
  85. pmc IKKalpha and IKKbeta regulation of DNA damage-induced cleavage of huntingtin
    Ali Khoshnan
    Biology Division 216 76, California Institute of Technology, Pasadena, California, USA
    PLoS ONE 4:e5768. 2009
    ..One stimulus may be the DNA damage that accumulates in neurons over time, and the subsequent activation of signaling pathways such as those regulated by IkappaB kinase (IKK), which can influence neurodegeneration in HD...
  86. doi High expression levels of IKKalpha and IKKbeta are necessary for the malignant properties of liver cancer
    Runqiu Jiang
    Liver Transplantation Center of the First Affiliated Hospital and Cancer Center, Nanjing Medical University, Nanjing, Jiangsu Province, People s Republic of China
    Int J Cancer 126:1263-74. 2010
    ..we analyzed the expression of mRNAs encoding components and targets of NF-kappaB signaling including IKKalpha, IKKbeta, RANK, RANKL, OPG, CyclinD3, mammary serine protease inhibitor (Maspin), CyclinD1, c-FLIP, Bcl-xl, Stat3, Cip1 ..
  87. pmc The IKK complex contributes to the induction of autophagy
    Alfredo Criollo
    INSERM, U848, Villejuif, France
    EMBO J 29:619-31. 2010
    ..Altogether, these results indicate that IKK has a cardinal role in the stimulation of autophagy by physiological and pharmacological stimuli...
  88. doi miR-218 inhibits the invasive ability of glioma cells by direct downregulation of IKK-β
    Libing Song
    State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Sun Yat sen University Cancer Center, Guangzhou, Guangdong 510060, China
    Biochem Biophys Res Commun 402:135-40. 2010
    ..Taken together, our results suggest that miR-218 plays an important role in preventing the invasiveness of glioma cells, and our results present a novel mechanism of miRNA-mediated direct suppression of IKK-β/NF-κB pathway in gliomas...
  89. doi SHARPIN is a component of the NF-κB-activating linear ubiquitin chain assembly complex
    Fuminori Tokunaga
    Department of Biophysics and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Osaka 565 0871, Japan
    Nature 471:633-6. 2011
    ....
  90. pmc Essential role for IKKβ in production of type 1 interferons by plasmacytoid dendritic cells
    Eduardo Pauls
    MRC Protein Phosphorylation Unit, The Sir James Black Centre, College of Life Sciences, University of Dundee, Scotland DD1 5EH, United Kingdom
    J Biol Chem 287:19216-28. 2012
    ....
  91. pmc Analysis of nuclear factor-κB (NF-κB) essential modulator (NEMO) binding to linear and lysine-linked ubiquitin chains and its role in the activation of NF-κB
    Tobias Kensche
    Buchmann Institute for Molecular Life Sciences and Institute of Biochemistry II, Goethe University School of Medicine, Theodor Stern Kai 7, D 60590 Frankfurt, Main, Germany
    J Biol Chem 287:23626-34. 2012
    ..This phenomenon could explain quantitatively distinct NF-κB activation patterns in response to numerous cell stimuli...
  92. pmc IκB kinase phosphorylation of SNAP-23 controls platelet secretion
    Zubair A Karim
    Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY 40536, USA
    Blood 121:4567-74. 2013
    ..In vivo studies with IKK inhibitors or platelet-specific IKK-β knockout mice showed that blocking IKK-β activity significantly prolonged tail bleeding times, suggesting that currently available IKK inhibitors may affect hemostasis...
  93. pmc A structural basis for IκB kinase 2 activation via oligomerization-dependent trans auto-phosphorylation
    Smarajit Polley
    Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, United States of America
    PLoS Biol 11:e1001581. 2013
    ..Here we report a 4 Å x-ray crystal structure of human IKK2 (hIKK2) in its catalytically active conformation...
  94. pmc Crystal structure of a human IκB kinase β asymmetric dimer
    Shenping Liu
    Structural Biology and Biophysics Group, Pfizer Worldwide Research, Groton, Connecticut 06340, USA
    J Biol Chem 288:22758-67. 2013
    ..The observed domain movements in the structures of IKKβ may represent trans-phosphorylation steps that accompany IKKβ activation. ..
  95. pmc Activation of the canonical IKK complex by K63/M1-linked hybrid ubiquitin chains
    Christoph H Emmerich
    Medical Research Council Protein Phosphorylation and Ubiquitylation Unit and Division of Cell Signaling and Immunology, Sir James Black Centre, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom
    Proc Natl Acad Sci U S A 110:15247-52. 2013
    ..Our study may help to resolve the debate about the relative importance of K63-pUb and M1-pUb chains in activating the canonical IKK complex. ..
  96. doi Deficiency of innate and acquired immunity caused by an IKBKB mutation
    Ulrich Pannicke
    From the Institute for Transfusion Medicine, University Hospital Ulm U P, C L, H S, K S, the Institute of Physiological Chemistry B B, T W, The Center for Biomedical Research, Genomics Core Facility K Holzmann, University of Ulm, and the Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Service Baden Wuerttemberg Hessen E M R, H S, K S, Ulm the Center of Chronic Immunodeficiency, University Medical Center Freiburg S F, P H, A R E, K Hese, M R, A J, M S, S E, The Faculty of Biology, University of Freiburg S F, the Center for Pediatrics and Adolescent Medicine P H, S E, and the Department of Rheumatology and Clinical Immunology M S, University Hospital Freiburg, Freiburg and the Translational Center for Regenerative Medicine, University of Leipzig, Leipzig S B all in Germany the Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institute
    N Engl J Med 369:2504-14. 2013
    ..Severe combined immunodeficiency (SCID) comprises a heterogeneous group of heritable deficiencies of humoral and cell-mediated immunity. Many patients with SCID have lymphocyte-activation defects that remain uncharacterized...
  97. ncbi Nuclear role of I kappa B Kinase-gamma/NF-kappa B essential modulator (IKK gamma/NEMO) in NF-kappa B-dependent gene expression
    Udit N Verma
    Division of Hematology Oncology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390 8594, USA
    J Biol Chem 279:3509-15. 2004
    The I kappa B kinase (IKK) complex, which is composed of the two kinases IKK alpha and IKK beta and the regulatory subunit IKK gamma/nuclear factor-kappa B (NF-kappa B) essential modulator (NEMO), is important in the cytokine-induced ..
  98. ncbi Expression of different NF-kappaB pathway genes in dendritic cells (DCs) or macrophages assessed by gene expression profiling
    I Baltathakis
    Medicine Hematology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229 3900, USA
    J Cell Biochem 83:281-90. 2001
    ..The results illustrate the ability of the NF-kappaB pathway to respond to differentiation stimuli by activating in a cell-specific manner unique signalling pathways and subsets of NF-kappaB target genes...
  99. pmc Lysyl oxidase inhibits ras-mediated transformation by preventing activation of NF-kappa B
    Sébastien Jeay
    Department of Biochemistry, Boston University Medical School, Boston, Massachusetts 02118, USA
    Mol Cell Biol 23:2251-63. 2003
    ..hypothesis, LO expression decreased both the rate of I kappa B alpha turnover and the activities of IKK alpha and IKK beta. Moreover, the ectopic expression of a constitutively active version of either kinase reversed the negative ..
  100. ncbi CD40-mediated activation of NF-kappa B in airway epithelial cells
    Stacie M Propst
    Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
    J Biol Chem 277:37054-63. 2002
    ..Moreover, these results suggest that CD40-mediated signaling in AEC differs with previously reported findings observed in other cell models, such as B lymphocytes...
  101. ncbi IKK beta is required for Bcl-2-mediated NF-kappa B activation in ventricular myocytes
    Kelly M Regula
    Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre, and the Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba R2H 2A6, Canada
    J Biol Chem 277:38676-82. 2002
    ..In view of growing evidence that the I kappa B kinases (IKKs), notably IKK beta, are involved in signal induced phosphorylation of I kappa B alpha, we ascertained whether IKK beta is necessary ..

Research Grants66

  1. MATTHEW PETER COGGINS; Fiscal Year: 2014
    ..This proposal seeks to investigate the role of IKKB and NF-kB signaling in the heart at baseline and under the stress of pressure overload...
  2. INDER MOHAN VERMA; Fiscal Year: 2014
    ..P53 and IKK2: We have found that IKK2, the key kinase in the NF-?B pathway, can also regulate the p53 stability by ..
  3. Negative regulation of NF-kB and inflammation by TAX1BP1
    Edward W Harhaj; Fiscal Year: 2012
    ..IKKa, but not IKKb or NEMO, is required for TNF-induced interactions among TAX1BP1, Itch, A20 and RIP1...
  4. Biochemical Characterization of Yersinia Effector YopJ
    Kim Orth; Fiscal Year: 2012
    ..The bacterial effector YopJ inhibits MAPK and NFkB signaling pathways by preventing activation of MKKs and IKKb. As described in our Progress Report, we discovered that the bacterial effector YopJ is an acetyltransferase that ..
  5. W Timothy Garvey; Fiscal Year: 2016
    ..These latter compounds activate various serine kinases, such as PKC or IKK2 (in association with activation of NF-:B), which then phosphorylate insulin receptor substrate (IRS) molecules ..
  6. Dongsheng Cai; Fiscal Year: 2016
    ..With the support of preliminary research that identified the role of hypothalamic IKK2/NF- :B in responding to nutrition and causing various whole-body physiological dysregulations, the long-term goal ..
  7. Dongsheng Cai; Fiscal Year: 2016
    ..Overall, successful completion of this project will significantly clarify the brain mechanism of obesity and T2D, and enlighten the development of interventional strategies against these diseases. ..
  8. Jianping Ye; Fiscal Year: 2015
    Title: Integration of IKK and JNK signals in Insulin Resistance ABSTRACT The serine kinases IKK2 and JNK1 contribute to insulin resistance by phosphorylation of IRS-1...
  9. ALBERT SIDNEY BALDWIN; Fiscal Year: 2014
    ..to xenografts and are quite limited regarding specific inhibitors, and do not focus on dual roles of IKK1 and IKK2. --To test our hypotheses, we propose to: (i) analyze basal-like cancer cells, animal models, and human tissue for ..
  10. Structural and functional studies of the IkappaB kinase (IKK) complex
    Hao Wu; Fiscal Year: 2013
    ..The intact IKK[unreadable] holo-complex is approximately 700-900kD in molecular mass containing multiple copies of IKK2 and NEMO...
  11. Integration of IKK and JNK signals in Insulin Resistance
    Jianping Ye; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The serine kinases IKK2 and JNK1 contribute to insulin resistance by phosphorylation of IRS-1...
  12. Astrocytes Play a Critical Role in the Pathology of EAE
    JOHN ROLAND BETHEA; Fiscal Year: 2013
    ..12xffIKKb) is obtained by breeding a GFAP-Cre line developed in Dr. Sofroniew's laboratory to a floxed (f/f) IKKb line generated in the laboratory of Dr. Michael Karin...
  13. Yousef Abu-Amer; Fiscal Year: 2016
    ..In fact, we discovered recently that constitutive activation of IKK2 is sufficient to induce RANKL-independent osteoclastogenesis in vitro...
  14. Paige C Geiger; Fiscal Year: 2014
    ..of HSP72 and HSP25 inhibit the stress kinases c-jun terminal kinase (JNK) and inhibitor of kappa B kinase 2 (IKK2), respectively, and improve insulin signaling in young (6- and 12-month-old) and aged (18- and 24-month-old) ..
  15. IKKbeta:Bi-Functional Regulator of Hepatocyte Proliferation
    Hyam L Leffert; Fiscal Year: 2010
    ..adult mouse liver regeneration is blunted and the incidence of HCC is attenuated in mice carrying cellular IKKB deletions throughout the liver including its hematopoietic cellular components...
  16. JOAN SAWYER STEFFAN; Fiscal Year: 2015
    ..Phosphorylation of serine (S) 13, a reaction which can be catalyzed by the kinase IKKb, in turn leads to phosphorylation of S16 and acetylation on lysine (K) 9...
  17. Study the roles of RNA editing enzyme ADAR1 in the regulation of cell death
    Qingde Wang; Fiscal Year: 2010
    ..The dynamic interaction of ADAR1 and IKK2 subunit upon cytokine stimulation will be defined...
  18. Role of a novel IKK-related kinase in inflammation
    SUSAN ELAINE SWEENEY; Fiscal Year: 2010
    ..NF-kB, in particular, plays a key role, and IkB kinase- 2 (IKK2) is an attractive therapeutic target. However, blockade of this kinase poses major safety concerns...
  19. Elucidating the Fas-activated inflammation-signaling complex (FISC)
    Mihail Iordanov; Fiscal Year: 2013
    ..the activation of the TGFb-Activated Kinase-1 (TAK1) and the Inhibitor of NF-kB-a (IkBa)-phosphorylating Kinase-b (IKKb)...
  20. Development and characterization of NIBP conditional knockout mice
    Wenhui Hu; Fiscal Year: 2011
    ..mechanism of potential human diseases caused by the loss or disruption of the target novel protein NIBP (NIK and IKK2-binding protein)...
  21. Yousef Abu-Amer; Fiscal Year: 2016
    ..The former pathway requires assembly of large IKK complex encompassing IKK1, IKK2, and IKK?, also known as NEMO...
  22. Mechanisms of RelA Activation in Cancer
    Paul J Chiao; Fiscal Year: 2013
    ..To test our related hypotheses, three specific aims were proposed: (1) Determine the role of IKK2-mediated NF-[unreadable]B activation in the development of pancreatic cancer using pancreatic specific IKK2 ..
  23. Targeting Inflammation using Salsalate in Type 1 Diabetic Neuropathy (TINSAL-T1DN
    RODICA contact POP-BUSUI; Fiscal Year: 2011
    ..It is a highly effective drug in blocking the IKK2/NF-:B pathway, with a large margin of safety, and low cost...
  24. Ann Richmond; Fiscal Year: 2016
    ..We have demonstrated that inhibiting IKK2, the major kinase that activates the canonical NF-?B pathway, in melanoma tumor bearing mice results in reduced ..
  25. Development and characterization of NIBP conditional knockout mice
    Wenhui Hu; Fiscal Year: 2012
    ..mechanism of potential human diseases caused by the loss or disruption of the target novel protein NIBP (NIK and IKK2-binding protein)...
  26. Pranoti Mandrekar; Fiscal Year: 2016
    ..Hsp90 from chronic alcohol-exposed macrophages associates with IKKb kinase, a pivotal kinase in NFkB activation and TNFa production...
  27. Jonathan P Katz; Fiscal Year: 2015
    ..on proliferation of keratinocytes from ED-L2/KLF4 mice~ and (c) crossing ED-L2/KLF4 mice with esophageal-specific Ikk2 null mice...
  28. Role of NADPH Oxidase in Regulating Inflammation
    Brahm H Segal; Fiscal Year: 2013
    ..aim 1: To test the hypothesis that NADPH oxidase attenuates NF-: activation by redox-sensitive suppression of IKK2 activity. Specific aim 2: To evaluate the interaction of NADPH oxidase and Nrf2 in regulating inflammation...
  29. Novel adamantyl arotinoids for the prevention and treatment of prostate cancer
    Francisco Javier Piedrafita; Fiscal Year: 2012
    ..Moreover, MX781 inhibits IKK2 in vitro and in cell-based assays...
  30. Targeting IKK beta and aurora kinases in melanoma
    Ann Richmond; Fiscal Year: 2013
    ..The data derived from this proposal will provide key insights for better design of clinical trials for melanoma patients which should positively impact our Veteran population. ..
  31. Assay Development for Screening of Specific IKKalpha Kinase Inhibitors
    Jun Li Luo; Fiscal Year: 2011
    DESCRIPTION (provided by applicant): Although IKK1 and IKK2 are highly homologous, their functions are very unique...
  32. Insulin Resistance in Tissue Specific IKKB Transgenics
    Jongsoon Lee; Fiscal Year: 2004
    Our studies in insulin resistant cells and animals, and type 2 diabetic patients showed that the IkappaB kinase, IKKbeta, plays a central role in acquired insulin resistance...
  33. Dongsheng Cai; Fiscal Year: 2016
    ..Overall, successful completion of this project will significantly clarify the brain mechanism of OHT, and enlighten the development of interventional strategies against OHT. ..
  34. TNF-Induced Apoptosis of Lymphocytes in Aged Humans
    Sudhir Gupta; Fiscal Year: 2004
    ..nuclear translocation by Confocal microscopy, [c] determine the expression (by Western blotting) and activation of IKKb (by IKK immune complex kinase assay using GST- IkBa with cytoplasmic extracts of TNR-treated T cells) following ..
  35. Feedback regulation of innate immune signaling at mucosal surfaces
    Derek Abbott; Fiscal Year: 2009
    ..protein, A20, is phosphorylated and activated by the central kinase in the NF-?B signaling pathway (IKK2). We mapped the site of phosphorylation and have shown that it is required for full A20 inhibitory activity...
  36. Role of IKK signaling in skeletal muscle atrophy
    Darin Van Gammeren; Fiscal Year: 2007
    ..the inhibitor of kB (IkB) retains Rel heterodimers in the cytosol until it is phosphorylated by IkB kinase beta (IKKB) and subsequently degraded...
  37. ANALYSIS OF HUMAN RAD51 RELATED PROTEINS
    David Schild; Fiscal Year: 2001
    ..If so, we will test if phosphorylation changes in response to x-ray or MMC treatment, and examine its biological significance by analyzing mutant Rad51C that may not be phosphorylated on key residues. ..
  38. Role of IKK-beta/NF-kappaB in hypothalamic dysregulation of energy balance
    Dongsheng Cai; Fiscal Year: 2007
    ..abstract_text> ..
  39. NF-kappaBeta activation T cell function/graft rejection
    Maria Luisa Alegre; Fiscal Year: 2006
    ..from CAR transgenic mice will be transduced with an adenoviral construct expressing a constitutively active form of IKKb. In all cases, effects on T cell survival, cytokine production, and differentiation into effector cells will be ..
  40. Mechanisms of IkappaB Kinase Regulation
    Ebrahim Zandi; Fiscal Year: 2006
    ..IKKy, which associates to IKKa and IKKbeta is a regulatory component required for signal-induced IKK activation...
  41. Estrogen Effects in Insulin Target and Granulosa Cells
    Jerrold Olefsky; Fiscal Year: 2004
    ..of the "inflammatory pathway" and that specific serine/ threonine kinases in this pathway such as PKC theta, IKK beta, or JNK, or genes induced as a result of NfkappaB activation, feedback on the insulin signaling system to cause ..
  42. Tissue-specific Overexpression of IKKbeta in mice
    PETER MELENDEZ; Fiscal Year: 2003
    DESCRIPTION: (Provided by Applicant) Recent studies from our laboratory suggest that the kB kinase, IKKb, may promote insulin resistance in obesity and patients with type 2 diabetes...
  43. IKK Beta In Intestinal Inflammation
    Laurence Egan; Fiscal Year: 2005
    ..hypothesis will be tested by studying the key molecule that activates NF-kappaB, inhibitory kappa B kinase beta (IKKbeta)...
  44. IN VIVO 2-COLOR BIOLUMINESCENT IMAGING OF CLASSICAL AND ALTERNATIVE NF-KB
    Deborah Novack; Fiscal Year: 2009
    ..In the classical pathway, ligand-induced activation of IKK2 leads to degradation of I?B1...
  45. REGULATION OF NF-KAPPA B
    Inder Verma; Fiscal Year: 2009
    ..We plan to understand the molecular function of the two kinases, IKK1 and IKK2 present in the IKK complex because they phosphorylate iKBcc at unique residues to trigger its degradation process...
  46. How Anthrax lethal factor kills activated macrophages
    Michael Karin; Fiscal Year: 2003
    ..anthracis and its host, this project should enable the design of new therapeutic strategies that will tilt the balance in favor of the host macrophage in the battle against B. anthracis and inhalation anthrax. ..
  47. Chemokines, nitric oxide, and myocardial depression
    Bysani Chandrasekar; Fiscal Year: 2005
    ..The results from these studies will further our knowledge of chemokine biology and lead to new therapeutic strategies to prevent or treat myocardial dysfunction in ischemia-reperfusion injury. ..
  48. Functions and Mechanisms of Radiation Induced Responses
    Michael Karin; Fiscal Year: 2006
    ..abstract_text> ..
  49. The Role of IKK2 in Osteoclastogenesis and Inflammatory Bone Destruction
    Jesse Otero; Fiscal Year: 2008
    ..inflammatory arthritis and periprosthetic osteolysis will be infected with viruses containing the mutant IKK-beta constructs to determine the effect of the IKK2 mutations in the setting of disease. [unreadable] [unreadable] [unreadable]
  50. How Anthrax lethal factor kills macrophages
    Michael Karin; Fiscal Year: 2008
    ..Interference with this activation process may be used to increase host resistance to bacterial infections, both with agents of bioterrorism and more common pathogens. ..
  51. INTERACTIONS OF HEAVY METAL IONS WITH THE HUMAN GENOME
    Michael Karin; Fiscal Year: 2007
    ..As NF-KB plays a key role in inflammation, understanding the regulation of IKK activity by oxidants, such as ozone, will provide a molecular basis for oxidant induced inflammatory disease. ..
  52. IKK MEDIATED INSULIN RESISTANCE AND IN VIVO REVERSAL
    Steven Shoelson; Fiscal Year: 2004
    ..abstract) This application is based on new data from the applicant's laboratory indicating that the protein kinase IKKb may act to inhibit the insulin signaling pathway...
  53. Ser/Thr Phosphorylation in Insulin Resistance
    Steven Shoelson; Fiscal Year: 2008
    ..These studies should provide a growing framework for understanding major mechanisms of insulin resistance in obesity, T2D and the metabolic syndrome. ..
  54. DIET AND SOMATIC MUTATIONS IN COLON CANCER
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2007
    ..e. p53, K-ras, and microsatellite instability). Differences in colon and rectal tumors will be compared. Additionally data from rectal tumors will be combined with that from colon tumors to define disease pathways. ..
  55. Growth Factors and Colon Cancer
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2006
    ..This study builds on a unique existing resource to study genetic and environmental associations with colorectal cancer. It will provide insight into colon cancer etiology and therefore avenues to disease prevention. ..
  56. REVERSAL OF MYOCARDIAL HYPERTROPHY IN HYPERTENSION
    Subha Sen; Fiscal Year: 2002
    ..On identifying the derangement, we will determine if appropriate treatment corrects the changes and if such directed alteration in myocardial collagen formation improves the compromised function of the hypertrophied heart. ..
  57. Immunogenetics of Non-Hodgkin Lymphoma Survival
    James Cerhan; Fiscal Year: 2006
    ..abstract_text> ..
  58. MAP KINASE ACTIVATION IN RSV-INDUCED CHEMOKINE SECRETION
    Antonella Casola; Fiscal Year: 2002
    ....
  59. A PROSPECTIVE STUDY OF ALASKA NATIVES & AMERICAN INDIANS
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2006
    ..The AIAN cohort will serve as a resource to enhance research and training activities of AIAN students interested in health research, health education, and general public health. ..
  60. FLOW SHEAR INDUCED NF-KB MEDIATED REGULATION
    Sumathy Mohan; Fiscal Year: 2003
    ..Understanding of NF- kappaB signaling mechanisms in VCAM-1 regulation can also be applied to other inflammatory conditions. ..
  61. FOUR-CORNERS BREAST AND ENDOMETRIAL CANCER STUDY
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2003
    ..C-peptide, glycosylated hemoglobin, IGF-1, and IGFBP3 will be evaluated with respect to breast and endometrial cancer in a subset of women. ..
  62. P21 transcriptional inhibitors as proapoptotic compounds
    Andrei Gartel; Fiscal Year: 2003
    ..This study may improve treatment of cancer by leading to the identification of new compounds that will increase the efficiency of cell death promoting anticancer drugs for cancer treatment. ..
  63. Using gene targeting to address the role of LRRK2 in Parkinson's disease
    Bruce Hostager; Fiscal Year: 2007
    ..This knowledge will aid in the identification of the environmental triggers and additional genetic factors that participate in the development of Parkinson's disease. ..
  64. Initiation of Cardiac Hypertrophy
    Subha Sen; Fiscal Year: 2008
    ..abstract_text> ..
  65. TOLL RECEPTOR ACTIVATION OF NF-kB IN INSULIN RESISTANCE AND T2DM
    Steven E Shoelson; Fiscal Year: 2010
    ..abstract_text> ..
  66. Molecular Epidemiology of non-Hodgkin Lymphoma Survival
    James R Cerhan; Fiscal Year: 2010
    ..Host genetics may also lead to a better understanding of NHL pathophysiology that could lead to new approaches to improve the survival of NHL patients. ..