4e3c

Structural highlights

Function

IKKB_HUMAN Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Also phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation.^{[1] [2] [3] [4] [5] [6]}

References

1. ↑ Salmeron A, Janzen J, Soneji Y, Bump N, Kamens J, Allen H, Ley SC. Direct phosphorylation of NF-kappaB1 p105 by the IkappaB kinase complex on serine 927 is essential for signal-induced p105 proteolysis. J Biol Chem. 2001 Jun 22;276(25):22215-22. Epub 2001 Apr 10. PMID:11297557 doi:10.1074/jbc.M101754200
2. ↑ Lobry C, Lopez T, Israel A, Weil R. Negative feedback loop in T cell activation through IkappaB kinase-induced phosphorylation and degradation of Bcl10. Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):908-13. Epub 2007 Jan 9. PMID:17213322 doi:10.1073/pnas.0606982104
3. ↑ Cui J, Zhu L, Xia X, Wang HY, Legras X, Hong J, Ji J, Shen P, Zheng S, Chen ZJ, Wang RF. NLRC5 negatively regulates the NF-kappaB and type I interferon signaling pathways. Cell. 2010 Apr 30;141(3):483-96. doi: 10.1016/j.cell.2010.03.040. PMID:20434986 doi:10.1016/j.cell.2010.03.040
4. ↑ Yoboua F, Martel A, Duval A, Mukawera E, Grandvaux N. Respiratory syncytial virus-mediated NF-kappa B p65 phosphorylation at serine 536 is dependent on RIG-I, TRAF6, and IKK beta. J Virol. 2010 Jul;84(14):7267-77. doi: 10.1128/JVI.00142-10. Epub 2010 Apr 21. PMID:20410276 doi:10.1128/JVI.00142-10
5. ↑ Tsuchiya Y, Asano T, Nakayama K, Kato T Jr, Karin M, Kamata H. Nuclear IKKbeta is an adaptor protein for IkappaBalpha ubiquitination and degradation in UV-induced NF-kappaB activation. Mol Cell. 2010 Aug 27;39(4):570-82. doi: 10.1016/j.molcel.2010.07.030. PMID:20797629 doi:10.1016/j.molcel.2010.07.030
6. ↑ Clark K, Peggie M, Plater L, Sorcek RJ, Young ER, Madwed JB, Hough J, McIver EG, Cohen P. Novel cross-talk within the IKK family controls innate immunity. Biochem J. 2011 Feb 15;434(1):93-104. doi: 10.1042/BJ20101701. PMID:21138416 doi:10.1042/BJ20101701