Activation of NF-kappaB in B cells

Fagerlund R, Melén K, Cao X, Julkunen I. NF-kappaB p52, RelB and c-Rel are transported into the nucleus via a subset of importin alpha molecules. Cell Signal. 2008 Aug;20(8):1442–51. doi: 10.1016/j.cellsig.2008.03.012. PMID: 18462924.; Ghosh CC, Vu HY, Mujo T, Vancurova I. Analysis of nucleocytoplasmic shuttling of NF kappa B proteins in human leukocytes. Methods Mol Biol. 2008;457():279–92. doi: 10.1007/978-1-59745-261-8_21. PMID: 19066035.; Tanner MJ, Hanel W, Gaffen SL, Lin X. CARMA1 coiled-coil domain is involved in the oligomerization and subcellular localization of CARMA1 and is required for T cell receptor-induced NF-kappaB activation. J Biol Chem. 2007 Jun 08;282(23):17141–7. doi: 10.1074/jbc.m700169200. PMID: 17428801.; Sommer K, Guo B, Pomerantz JL, Bandaranayake AD, Moreno-García ME, Ovechkina YL, Rawlings DJ. Phosphorylation of the CARMA1 linker controls NF-kappaB activation. Immunity. 2005 Dec;23(6):561–74. doi: 10.1016/j.immuni.2005.09.014. PMID: 16356855.; Shinohara H, Yasuda T, Aiba Y, Sanjo H, Hamadate M, Watarai H, Sakurai H, Kurosaki T. PKC beta regulates BCR-mediated IKK activation by facilitating the interaction between TAK1 and CARMA1. J Exp Med. 2005 Nov 21;202(10):1423–31. PMID: 16301747; PMCID: PMC2212994.; Wang C, Deng L, Hong M, Akkaraju GR, Inoue J, Chen ZJ. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature. 2001 Jul 19;412(6844):346–51. doi: 10.1038/35085597. PMID: 11460167.; Burke JR, Wood MK, Ryseck RP, Walther S, Meyers CA. Peptides corresponding to the N and C termini of IkappaB-alpha, -beta, and -epsilon as probes of the two catalytic subunits of IkappaB kinase, IKK-1 and IKK-2. J Biol Chem. 1999 Dec 17;274(51):36146–52. doi: 10.1074/jbc.274.51.36146. PMID: 10593898.; Heilker R, Freuler F, Pulfer R, Di Padova F, Eder J. All three IkappaB isoforms and most Rel family members are stably associated with the IkappaB kinase 1/2 complex. Eur J Biochem. 1999 Jan;259(1-2):253–61. doi: 10.1046/j.1432-1327.1999.00028.x. PMID: 9914500.; Zandi E, Chen Y, Karin M. Direct phosphorylation of IkappaB by IKKalpha and IKKbeta: discrimination between free and NF-kappaB-bound substrate. Science. 1998 Aug 28;281(5381):1360–3. doi: 10.1126/science.281.5381.1360. PMID: 9721103.; Scherer DC, Brockman JA, Chen Z, Maniatis T, Ballard DW. Signal-induced degradation of I kappa B alpha requires site-specific ubiquitination. Proc. Natl. Acad. Sci. U.S.A. 1995 Nov 21;92(24):11259–63. doi: 10.1073/pnas.92.24.11259.; Alkalay I, Yaron A, Hatzubai A, Orian A, Ciechanover A, Ben-Neriah Y. Stimulation-dependent I kappa B alpha phosphorylation marks the NF-kappa B inhibitor for degradation via the ubiquitin-proteasome pathway. Proc. Natl. Acad. Sci. U.S.A. 1995 Nov 07;92(23):10599–603. doi: 10.1073/pnas.92.23.10599.; Li CC, Dai RM, Longo DL. Inactivation of NF-kappa B inhibitor I kappa B alpha: ubiquitin-dependent proteolysis and its degradation product. Biochem Biophys Res Commun. 1995 Oct 04;215(1):292–301. doi: 10.1006/bbrc.1995.2465. PMID: 7575604.; Chen Z, Hagler J, Palombella VJ, Melandri F, Scherer D, Ballard D, Maniatis T. Signal-induced site-specific phosphorylation targets I kappa B alpha to the ubiquitin-proteasome pathway. Genes Dev. 1995 Jul 01;9(13):1586–97. doi: 10.1101/gad.9.13.1586. PMID: 7628694.; DiDonato JA, Mercurio F, Karin M. Phosphorylation of I kappa B alpha precedes but is not sufficient for its dissociation from NF-kappa B. Mol Cell Biol. 1995 Mar;15(3):1302–11. PMID: 7862124; PMCID: PMC230353.; Lin YC, Brown K, Siebenlist U. Activation of NF-kappa B requires proteolysis of the inhibitor I kappa B-alpha: signal-induced phosphorylation of I kappa B-alpha alone does not release active NF-kappa B. Proc. Natl. Acad. Sci. U.S.A. 1995 Jan 17;92(2):552–6. doi: 10.1073/pnas.92.2.552.; Miyamoto S, Maki M, Schmitt MJ, Hatanaka M, Verma IM. Tumor necrosis factor alpha-induced phosphorylation of I kappa B alpha is a signal for its degradation but not dissociation from NF-kappa B. Proc. Natl. Acad. Sci. U.S.A. 1994 Dec 20;91(26):12740–4. doi: 10.1073/pnas.91.26.12740.; Traenckner EB, Wilk S, Baeuerle PA. A proteasome inhibitor prevents activation of NF-kappa B and stabilizes a newly phosphorylated form of I kappa B-alpha that is still bound to NF-kappa B. The EMBO Journal. 1994 Nov;13(22):5433–41. doi: 10.1002/j.1460-2075.1994.tb06878.x.; Kochs G, Hummel R, Fiebich B, Sarre TF, Marmé D, Hug H. Activation of purified human protein kinase C alpha and beta I isoenzymes in vitro by Ca2+, phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate. Biochem J. 1993 Apr 15;291 ( Pt 2)():627–33. PMID: 8387275; PMCID: PMC1132570.; Blank V, Kourilsky P, Israël A. Cytoplasmic retention, DNA binding and processing of the NF-kappa B p50 precursor are controlled by a small region in its C-terminus. The EMBO Journal. 1991 Dec;10(13):4159–67. doi: 10.1002/j.1460-2075.1991.tb04994.x.; Baeuerle PA, Baltimore D. Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-kappa B transcription factor. Cell. 1988 Apr 22;53(2):211–7. doi: 10.1016/0092-8674(88)90382-0. PMID: 3129195.

Metabolites

Calcium cation

Formula: Ca (39.962591)

CAS ID: 14127-61-8

ATP(4-)

Formula: C10H12N5O13P3 (502.9644492)

CAS ID:

ADP(3-)

Formula: C10H12N5O10P2 (424.0059412)

CAS ID:



Enzyme

EC Number name full name note
2.7.11.1 non-specific serine/threonine protein kinase ATP:protein phosphotransferase (non-specific)
2.7.11.10 IkappaB kinase ATP:[IkappaB protein] phosphotransferase
2.7.11.13 protein kinase C ATP:protein phosphotransferase (diacylglycerol-dependent)


Proteins

Protein ID name full name