Reactome | Activation of NF-kappaB in B cells

Activation of NF-kappaB in B cells

Stable Identifier

R-HSA-1169091

Type

Pathway

Species

Homo sapiens

Compartment

cytosol, nucleoplasm, plasma membrane

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DAG and calcium activate protein kinase C beta (PKC-beta, Kochs et al. 1991) which phosphorylates CARMA1 and other proteins (Sommer et al. 2005). Phosphorylated CARMA1 recruits BCL10 and MALT1 to form the CBM complex (Sommer et al. 2005, Tanner et al. 2007) which, in turn, recruits the kinase TAK1 and the IKK complex (Sommer et al. 2005, Shinohara et al. 2005 using chicken cells). TAK1 phosphorylates the IKK-beta subunit, activating it (Wang et al. 2001). The IKK complex then phosphorylates IkB complexed with NF-kappaB dimers in the cytosol (Zandi et al. 1998, Burke et al. 1999, Heilker et al. 1999), resulting in the degradation of IkB (Miyamoto et al. 1994, Traenckner et al. 1994, Alkalay et al. 1995, DiDonato et al. 1995, Li et al. 1995, Lin et al. 1995, Scherer et al. 1995, Chen et al. 1995). NF-kappaB dimers are thereby released and are translocated to the nucleus where they activate transcription (Baeuerle and Baltimore 1988, Blank et al. 1991, Ghosh et al. 2008, Fagerlund et al. 2008).

Literature References

PubMed ID	Title	Journal	Year
7479848	Stimulation-dependent I kappa B alpha phosphorylation marks the NF-kappa B inhibitor for degradation via the ubiquitin-proteasome pathway Ciechanover, A, Hatzubai, A, Alkalay, I, Yaron, A, Orian, A, Ben-Neriah, Y	Proc Natl Acad Sci U S A	1995
7831327	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 Lin, YC, Siebenlist, U, Brown, K	Proc Natl Acad Sci U S A	1995
7628694	Signal-induced site-specific phosphorylation targets I kappa B alpha to the ubiquitin-proteasome pathway Scherer, D, Chen, Z, Hagler, J, Palombella, VJ, Ballard, D, Maniatis, T, Melandri, F	Genes Dev	1995
16301747	PKC beta regulates BCR-mediated IKK activation by facilitating the interaction between TAK1 and CARMA1 Shinohara, H, Sakurai, H, Sanjo, H, Aiba, Y, Hamadate, M, Yasuda, T, Watarai, H, Kurosaki, T	J Exp Med	2005
18462924	NF-kappaB p52, RelB and c-Rel are transported into the nucleus via a subset of importin alpha molecules Cao, X, Melén, K, Fagerlund, R, Julkunen, I	Cell Signal	2008
9721103	Direct phosphorylation of IkappaB by IKKalpha and IKKbeta: discrimination between free and NF-kappaB-bound substrate Karin, M, Zandi, E, Chen, Y	Science	1998
16356855	Phosphorylation of the CARMA1 linker controls NF-kappaB activation Sommer, K, Pomerantz, JL, Rawlings, DJ, Guo, B, Bandaranayake, AD, Ovechkina, YL, Moreno-Garcia, ME	Immunity	2005
17428801	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 Tanner, MJ, Lin, X, Gaffen, SL, Hanel, W	J Biol Chem	2007
7479976	Signal-induced degradation of I kappa B alpha requires site-specific ubiquitination Chen, Z, Brockman, JA, Scherer, DC, Ballard, DW, Maniatis, T	Proc Natl Acad Sci U S A	1995
3129195	Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-kappa B transcription factor Baltimore, D, Baeuerle, PA	Cell	1988
7862124	Phosphorylation of I kappa B alpha precedes but is not sufficient for its dissociation from NF-kappa B Karin, M, DiDonato, JA, Mercurio, F	Mol Cell Biol	1995
7809113	Tumor necrosis factor alpha-induced phosphorylation of I kappa B alpha is a signal for its degradation but not dissociation from NF-kappa B Hatanaka, M, Maki, M, Miyamoto, S, Verma, IM, Schmitt, MJ	Proc Natl Acad Sci U S A	1994
10593898	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 Burke, JR, Wood, MK, Walther, S, Meyers, CA, Ryseck, RP	J Biol Chem	1999
7957109	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 Wilk, S, Baeuerle, PA, Traenckner, EB	EMBO J	1994
1756723	Cytoplasmic retention, DNA binding and processing of the NF-kappa B p50 precursor are controlled by a small region in its C-terminus Blank, V, Kourilsky, P, Israel, A	EMBO J	1991
8387275	Activation of purified human protein kinase C alpha and beta I isoenzymes in vitro by Ca2+, phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate Hummel, R, Marmé, D, Sarre, TF, Fiebich, B, Hug, H, Kochs, G	Biochem J	1993
9914500	All three IkappaB isoforms and most Rel family members are stably associated with the IkappaB kinase 1/2 complex Pulfer, R, Eder, J, di Padova, F, Heilker, R, Freuler, F	Eur J Biochem	1999
7575604	Inactivation of NF-kappa B inhibitor I kappa B alpha: ubiquitin-dependent proteolysis and its degradation product Dai, RM, Li, CC, Longo, DL	Biochem Biophys Res Commun	1995
19066035	Analysis of nucleocytoplasmic shuttling of NF kappa B proteins in human leukocytes Ghosh, CC, Vu, HY, Mujo, T, Vancurova, I	Methods Mol Biol	2008
11460167	TAK1 is a ubiquitin-dependent kinase of MKK and IKK Deng, L, Inoue, J, Akkaraju, GR, Hong, M, Wang, C, Chen, ZJ	Nature	2001