IKK2

Inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta

Rendering based on PDB 3BRT.
Identifiers
Symbols IKBKB; FLJ33771; FLJ36218; FLJ38368; FLJ40509; IKK-beta; IKK2; IKKB; MGC131801; NFKBIKB
External IDs OMIM: 603258 MGI: 1338071 HomoloGene: 7782 GeneCards: IKBKB Gene
EC number 2.7.11.10
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 3551 16150
Ensembl ENSG00000104365 ENSMUSG00000031537
UniProt O14920 Q05DR8
RefSeq (mRNA) NM_001190720.1 NM_010546
RefSeq (protein) NP_001177649.1 NP_034676
Location (UCSC) Chr 8:
42.13 – 42.19 Mb		 Chr 8:
23.77 – 23.82 Mb
PubMed search [1] [2]

IKK-β also known as inhibitor of nuclear factor kappa-B kinase subunit beta is a protein that in humans is encoded by the IKBKB (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta) gene.

Contents

Function

Main article: IκB kinase

IKK-β is an enzyme that serves as a protein subunit of IκB kinase, which is a component of the cytokine-activated intracellular signaling pathway involved in triggering immune responses. Its activity causes activation of a transcription factor known as Nuclear Transcription factor kappa-B or NF-κB. Activated IKK-β phosphorylates a protein called the inhibitor of NF-κB, IκB (IκBα), which binds NF-κB to inhibit its function. Phosphorylated IκB is degraded via the ubiquitination pathway, freeing NF-κB, and allowing its entry into the nucleus of the cell where it activates various genes involved in inflammation and other immune responses.

Clinical significance

IKK-β plays a significant role in brain cells following a stroke. citation needed, Oct 2011. If NF-κB inhibition by IKK-β is blocked, damaged cells within the brain stay alive, and according to a study performed by the University of Heidelberg and the University of Ulm, the cells even appear to make some recovery.[1] The size of the infarct, or tissue killed or damaged by ischemia, is reduced in mice in which IKK-β has been blocked.[2] Additionally, experimental mice with an overactive form of IKK-β experience loss of many more neurons than normal mice after a stroke-simulating event.[1] Researchers found a molecule that could block the signaling of IKK-β for up to four and a half hours.[3] In another study, researchers found that inhibiting IKK-β prevented kidney and wasting diseases in an animal model used to study wasting diseases of human AIDS sufferers.[4]

Interactions

IKK-β (IKBKB) has been shown to interact with

References

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  4. ^ Heckmann A, Waltzinger C, Jolicoeur P, Dreano M, Kosco-Vilbois MH, and Sagot Y. 2004. IKK-β Inhibitor Alleviates Kidney and Wasting Diseases in a Murine Model of Human AIDS. American Journal of Pathology. Volume 164, Pages 1253-1262. Retrieved on June 30, 2007.
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  14. ^ a b Wu, Ray-Chang; Qin Jun, Hashimoto Yoshihiro, Wong Jiemin, Xu Jianming, Tsai Sophia Y, Tsai Ming-Jer, O'Malley Bert W (May. 2002). "Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) Coactivator Activity by IκB Kinase". Mol. Cell. Biol. (United States) 22 (10): 3549–61. doi:10.1128/MCB.22.10.3549-3561.2002. ISSN 0270-7306. PMC 133790. PMID 11971985. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=133790. 
  15. ^ Shifera, Amde Selassie; Horwitz Marshall S (Mar. 2008). "Mutations in the zinc finger domain of IKK gamma block the activation of NF-kappa B and the induction of IL-2 in stimulated T lymphocytes". Mol. Immunol. (England) 45 (6): 1633–45. doi:10.1016/j.molimm.2007.09.036. ISSN 0161-5890. PMID 18207244. 
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  24. ^ Zhang, S Q; Kovalenko A, Cantarella G, Wallach D (Mar. 2000). "Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation". Immunity (UNITED STATES) 12 (3): 301–11. doi:10.1016/S1074-7613(00)80183-1. ISSN 1074-7613. PMID 10755617. 
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See also