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Gene Review

IKBKB  -  inhibitor of kappa light polypeptide gene...

Homo sapiens

Synonyms: I-kappa-B kinase 2, I-kappa-B-kinase beta, IKK-B, IKK-beta, IKK2, ...
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Disease relevance of IKBKB


High impact information on IKBKB


Chemical compound and disease context of IKBKB


Biological context of IKBKB


Anatomical context of IKBKB

  • As such, IKKbeta-mediated phosphorylation of IKKgamma at these specific serine targets may facilitate proper regulation of NF-kappaB signaling in the immune system [17].
  • Validation of the anti-inflammatory properties of small-molecule IkappaB Kinase (IKK)-2 inhibitors by comparison with adenoviral-mediated delivery of dominant-negative IKK1 and IKK2 in human airways smooth muscle [18].
  • Endothelial IKK beta signaling is required for monocyte adhesion under laminar flow conditions [19].
  • We conclude that IKK beta is necessary for the cytokine-induced inflammatory phenotype of human endothelium and endothelial recruitment of human monocytes under flow [19].
  • Differential expression of NF-kappaB pathway intermediates occurred when progesterone concentrations increased in early pregnancy; IKKalpha and NIK mRNA levels increased in decidua whilst IKKbeta and MEKK1 mRNA levels declined [20].

Associations of IKBKB with chemical compounds


Physical interactions of IKBKB


Enzymatic interactions of IKBKB

  • MLK3 directly phosphorylated and thus activated IkappaB kinase alpha (IKKalpha) and IKKbeta, revealing its function as an IkappaB kinase kinase (IKKK) [29].
  • In addition to TBK1 and IKKepsilon, our results indicate that IKKbeta can also phosphorylate IRF-3 and activate the IFN-stimulated response element [30].
  • Recombinant IKKbeta also phosphorylated Dok1 or Dok1 amino acids 430-481 in vitro [31].
  • These results indicate that IKKalpha, in addition to its previously described ability to phosphorylate IkappaBalpha, can increase the ability of IKKbeta to phosphorylate IkappaBalpha [32].

Co-localisations of IKBKB


Regulatory relationships of IKBKB


Other interactions of IKBKB

  • IKK is made up of two kinases, IKK-alpha and IKK-beta, which phosphorylate I(kappa)B, leading to its degradation and translocation of NF-kappaB to the nucleus [21].
  • Because the IKKs have previously been demonstrated to associate with the nuclear hormone receptor coactivator AIB1/SRC-3, the question of whether either IKKalpha or IKKbeta may be involved in increasing the expression of hormone-responsive genes was addressed [38].
  • We also show that MEKK1 can induce the activation of both IKK-alpha and IKK-beta in vivo [39].
  • Furthermore, genes suppressed by IKK2/NF-kappa B were newly identified [40].
  • IKK contains two structurally related catalytic subunits termed IKKalpha and IKKbeta as well as a noncatalytic subunit called IKKgamma/NEMO [17].

Analytical, diagnostic and therapeutic context of IKBKB


  1. Role of inflammatory mediators in the suppression of insulin receptor phosphorylation in circulating mononuclear cells of obese subjects. Ghanim, H., Aljada, A., Daoud, N., Deopurkar, R., Chaudhuri, A., Dandona, P. Diabetologia (2007) [Pubmed]
  2. IkappaB kinase complex is an intracellular target for endotoxic lipopolysaccharide in human monocytic cells. Hawiger, J., Veach, R.A., Liu, X.Y., Timmons, S., Ballard, D.W. Blood (1999) [Pubmed]
  3. Sulfasalazine and BAY 11-7082 interfere with the nuclear factor-kappa B and I kappa B kinase pathway to regulate the release of proinflammatory cytokines from human adipose tissue and skeletal muscle in vitro. Lappas, M., Yee, K., Permezel, M., Rice, G.E. Endocrinology (2005) [Pubmed]
  4. Sustained activation of protein kinase C downregulates nuclear factor-{kappa}B signaling by dissociation of IKK-{gamma} and Hsp90 complex in human colonic epithelial cells. Park, K.A., Byun, H.S., Won, M., Yang, K.J., Shin, S., Piao, L., Kim, J.M., Yoon, W.H., Junn, E., Park, J., Seok, J.H., Hur, G.M. Carcinogenesis (2007) [Pubmed]
  5. H. pylori activates NF-kappaB through a signaling pathway involving IkappaB kinases, NF-kappaB-inducing kinase, TRAF2, and TRAF6 in gastric cancer cells. Maeda, S., Yoshida, H., Ogura, K., Mitsuno, Y., Hirata, Y., Yamaji, Y., Akanuma, M., Shiratori, Y., Omata, M. Gastroenterology (2000) [Pubmed]
  6. Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Karin, M., Ben-Neriah, Y. Annu. Rev. Immunol. (2000) [Pubmed]
  7. HTLV-I Tax protein binds to MEKK1 to stimulate IkappaB kinase activity and NF-kappaB activation. Yin, M.J., Christerson, L.B., Yamamoto, Y., Kwak, Y.T., Xu, S., Mercurio, F., Barbosa, M., Cobb, M.H., Gaynor, R.B. Cell (1998) [Pubmed]
  8. The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation. Zandi, E., Rothwarf, D.M., Delhase, M., Hayakawa, M., Karin, M. Cell (1997) [Pubmed]
  9. Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IkappaB kinase. Rossi, A., Kapahi, P., Natoli, G., Takahashi, T., Chen, Y., Karin, M., Santoro, M.G. Nature (2000) [Pubmed]
  10. Prolyl hydroxylase-1 negatively regulates I{kappa}B kinase-beta, giving insight into hypoxia-induced NF{kappa}B activity. Cummins, E.P., Berra, E., Comerford, K.M., Ginouves, A., Fitzgerald, K.T., Seeballuck, F., Godson, C., Nielsen, J.E., Moynagh, P., Pouyssegur, J., Taylor, C.T. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  11. Fluticasone reduces IL-6 and IL-8 production of cystic fibrosis bronchial epithelial cells via IKK-beta kinase pathway. Escotte, S., Tabary, O., Dusser, D., Majer-Teboul, C., Puchelle, E., Jacquot, J. Eur. Respir. J. (2003) [Pubmed]
  12. Sulindac inhibits activation of the NF-kappaB pathway. Yamamoto, Y., Yin, M.J., Lin, K.M., Gaynor, R.B. J. Biol. Chem. (1999) [Pubmed]
  13. Localization of the human I-kappaB kinase-beta (IKBKB) to chromosome 8p11.2 by fluorescence in situ hybridization and radiation hybrid mapping. Ambros, P.F., Schmid, J., Rumpler, S., Binder, B.R., de Martin, R. Genomics (1998) [Pubmed]
  14. Assignment of IkappaB kinase beta (IKBKB) to human chromosome band 8p12-->p11 by in situ hybridization. Shindo, M., Nakano, H., Sakon, S., Yagita, H., Mihara, M., Okumura, K. Cytogenet. Cell Genet. (1998) [Pubmed]
  15. TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90. Chen, G., Cao, P., Goeddel, D.V. Mol. Cell (2002) [Pubmed]
  16. 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 (TBK1), and an unknown kinase and couples p65 to TATA-binding protein-associated factor II31-mediated interleukin-8 transcription. Buss, H., Dörrie, A., Schmitz, M.L., Hoffmann, E., Resch, K., Kracht, M. J. Biol. Chem. (2004) [Pubmed]
  17. In vivo identification of inducible phosphoacceptors in the IKKgamma/NEMO subunit of human IkappaB kinase. Carter, R.S., Pennington, K.N., Ungurait, B.J., Ballard, D.W. J. Biol. Chem. (2003) [Pubmed]
  18. Validation of the anti-inflammatory properties of small-molecule IkappaB Kinase (IKK)-2 inhibitors by comparison with adenoviral-mediated delivery of dominant-negative IKK1 and IKK2 in human airways smooth muscle. Catley, M.C., Sukkar, M.B., Chung, K.F., Jaffee, B., Liao, S.M., Coyle, A.J., Haddad, e.l.-.B., Barnes, P.J., Newton, R. Mol. Pharmacol. (2006) [Pubmed]
  19. Endothelial IKK beta signaling is required for monocyte adhesion under laminar flow conditions. Meiler, S.E., Hung, R.R., Gerszten, R.E., Gianetti, J., Li, L., Matsui, T., Gimbrone, M.A., Rosenzweig, A. J. Mol. Cell. Cardiol. (2002) [Pubmed]
  20. The NF-kappaB pathway in human endometrium and first trimester decidua. King, A.E., Critchley, H.O., Kelly, R.W. Mol. Hum. Reprod. (2001) [Pubmed]
  21. The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta. Yin, M.J., Yamamoto, Y., Gaynor, R.B. Nature (1998) [Pubmed]
  22. c-Src-dependent tyrosine phosphorylation of IKKbeta is involved in tumor necrosis factor-alpha-induced intercellular adhesion molecule-1 expression. Huang, W.C., Chen, J.J., Chen, C.C. J. Biol. Chem. (2003) [Pubmed]
  23. Dbl and the Rho GTPases activate NF kappa B by I kappa B kinase (IKK)-dependent and IKK-independent pathways. Cammarano, M.S., Minden, A. J. Biol. Chem. (2001) [Pubmed]
  24. Suppression of NF-kappaB and NF-kappaB-regulated gene expression by sulforaphane and PEITC through IkappaBalpha, IKK pathway in human prostate cancer PC-3 cells. Xu, C., Shen, G., Chen, C., Gélinas, C., Kong, A.N. Oncogene (2005) [Pubmed]
  25. CIKS, a connection to Ikappa B kinase and stress-activated protein kinase. Leonardi, A., Chariot, A., Claudio, E., Cunningham, K., Siebenlist, U. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  26. IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK. Woronicz, J.D., Gao, X., Cao, Z., Rothe, M., Goeddel, D.V. Science (1997) [Pubmed]
  27. PKR stimulates NF-kappaB irrespective of its kinase function by interacting with the IkappaB kinase complex. Bonnet, M.C., Weil, R., Dam, E., Hovanessian, A.G., Meurs, E.F. Mol. Cell. Biol. (2000) [Pubmed]
  28. Protein phosphatase 2Cbeta association with the IkappaB kinase complex is involved in regulating NF-kappaB activity. Prajapati, S., Verma, U., Yamamoto, Y., Kwak, Y.T., Gaynor, R.B. J. Biol. Chem. (2004) [Pubmed]
  29. Mixed-lineage kinase 3 delivers CD3/CD28-derived signals into the IkappaB kinase complex. Hehner, S.P., Hofmann, T.G., Ushmorov, A., Dienz, O., Wing-Lan Leung, I., Lassam, N., Scheidereit, C., Dröge, W., Schmitz, M.L. Mol. Cell. Biol. (2000) [Pubmed]
  30. Mechanisms of the TRIF-induced interferon-stimulated response element and NF-kappaB activation and apoptosis pathways. Han, K.J., Su, X., Xu, L.G., Bin, L.H., Zhang, J., Shu, H.B. J. Biol. Chem. (2004) [Pubmed]
  31. IkappaB kinase beta phosphorylates Dok1 serines in response to TNF, IL-1, or gamma radiation. Lee, S., Andrieu, C., Saltel, F., Destaing, O., Auclair, J., Pouchkine, V., Michelon, J., Salaun, B., Kobayashi, R., Jurdic, P., Kieff, E.D., Sylla, B.S. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  32. IkappaB kinase alpha (IKKalpha) regulation of IKKbeta kinase activity. Yamamoto, Y., Yin, M.J., Gaynor, R.B. Mol. Cell. Biol. (2000) [Pubmed]
  33. The N-terminus of PKR is responsible for the activation of the NF-kappaB signaling pathway by interacting with the IKK complex. Bonnet, M.C., Daurat, C., Ottone, C., Meurs, E.F. Cell. Signal. (2006) [Pubmed]
  34. Primary human CD4+ T cells contain heterogeneous I kappa B kinase complexes: role in activation of the IL-2 promoter. Khoshnan, A., Kempiak, S.J., Bennett, B.L., Bae, D., Xu, W., Manning, A.M., June, C.H., Nel, A.E. J. Immunol. (1999) [Pubmed]
  35. The Jun kinase cascade is responsible for activating the CD28 response element of the IL-2 promoter: proof of cross-talk with the I kappa B kinase cascade. Kempiak, S.J., Hiura, T.S., Nel, A.E. J. Immunol. (1999) [Pubmed]
  36. Heterogeneous requirement of IkappaB kinase 2 for inflammatory cytokine and matrix metalloproteinase production in rheumatoid arthritis: implications for therapy. Andreakos, E., Smith, C., Kiriakidis, S., Monaco, C., de Martin, R., Brennan, F.M., Paleolog, E., Feldmann, M., Foxwell, B.M. Arthritis Rheum. (2003) [Pubmed]
  37. IKKalpha regulates mitogenic signaling through transcriptional induction of cyclin D1 via Tcf. Albanese, C., Wu, K., D'Amico, M., Jarrett, C., Joyce, D., Hughes, J., Hulit, J., Sakamaki, T., Fu, M., Ben-Ze'ev, A., Bromberg, J.F., Lamberti, C., Verma, U., Gaynor, R.B., Byers, S.W., Pestell, R.G. Mol. Biol. Cell (2003) [Pubmed]
  38. Formation of an IKKalpha-dependent transcription complex is required for estrogen receptor-mediated gene activation. Park, K.J., Krishnan, V., O'Malley, B.W., Yamamoto, Y., Gaynor, R.B. Mol. Cell (2005) [Pubmed]
  39. MEKK1 activates both IkappaB kinase alpha and IkappaB kinase beta. Lee, F.S., Peters, R.T., Dang, L.C., Maniatis, T. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  40. Transcriptional profiling of IKK2/NF-kappa B- and p38 MAP kinase-dependent gene expression in TNF-alpha-stimulated primary human endothelial cells. Viemann, D., Goebeler, M., Schmid, S., Klimmek, K., Sorg, C., Ludwig, S., Roth, J. Blood (2004) [Pubmed]
  41. NF-kappa B regulation by I kappa B kinase in primary fibroblast-like synoviocytes. Aupperle, K.R., Bennett, B.L., Boyle, D.L., Tak, P.P., Manning, A.M., Firestein, G.S. J. Immunol. (1999) [Pubmed]
  42. The kinetics of association and phosphorylation of IkappaB isoforms by IkappaB kinase 2 correlate with their cellular regulation in human endothelial cells. Heilker, R., Freuler, F., Vanek, M., Pulfer, R., Kobel, T., Peter, J., Zerwes, H.G., Hofstetter, H., Eder, J. Biochemistry (1999) [Pubmed]
  43. Elevated constitutive IkappaB kinase activity and IkappaB-alpha phosphorylation in Hs294T melanoma cells lead to increased basal MGSA/GRO-alpha transcription. Devalaraja, M.N., Wang, D.Z., Ballard, D.W., Richmond, A. Cancer Res. (1999) [Pubmed]
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