Reactome: A Curated Pathway Database

Activation of NF-kappaB in B cells

Stable Identifier
Homo sapiens
Locations in the PathwayBrowser

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
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 Proc Natl Acad Sci U S A 1995
7479848 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
7628694 Signal-induced site-specific phosphorylation targets I kappa B alpha to the ubiquitin-proteasome pathway Genes Dev 1995
16301747 PKC beta regulates BCR-mediated IKK activation by facilitating the interaction between TAK1 and CARMA1 J Exp Med 2005
18462924 NF-kappaB p52, RelB and c-Rel are transported into the nucleus via a subset of importin alpha molecules Cell Signal 2008
9721103 Direct phosphorylation of IkappaB by IKKalpha and IKKbeta: discrimination between free and NF-kappaB-bound substrate Science 1998
16356855 Phosphorylation of the CARMA1 linker controls NF-kappaB activation 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 J Biol Chem 2007
7479976 Signal-induced degradation of I kappa B alpha requires site-specific ubiquitination 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 Cell 1988
7862124 Phosphorylation of I kappa B alpha precedes but is not sufficient for its dissociation from NF-kappa B 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 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 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 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 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 Biochem J 1993
9914500 All three IkappaB isoforms and most Rel family members are stably associated with the IkappaB kinase 1/2 complex Eur J Biochem 1999
7575604 Inactivation of NF-kappa B inhibitor I kappa B alpha: ubiquitin-dependent proteolysis and its degradation product Biochem Biophys Res Commun 1995
19066035 Analysis of nucleocytoplasmic shuttling of NF kappa B proteins in human leukocytes Methods Mol Biol 2008
11460167 TAK1 is a ubiquitin-dependent kinase of MKK and IKK Nature 2001
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