KEGG   PATHWAY: mmu04064
Entry
mmu04064                    Pathway                                
Name
NF-kappa B signaling pathway - Mus musculus (house mouse)
Description
Nuclear factor-kappa B (NF-kappa B) is the generic name of a family of transcription factors that function as dimers and regulate genes involved in immunity, inflammation and cell survival. There are several pathways leading to NF-kappa B-activation. The canonical pathway is induced by tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) or byproducts of bacterial and viral infections. This pathway relies on IKK- mediated IkappaB-alpha phosphorylation on Ser32 and 36, leading to its degradation, which allows the p50/p65 NF-kappa B dimer to enter the nucleus and activate gene transcription. Atypical pathways are IKK-independent and rely on phosphorylation of IkappaB-alpha on Tyr42 or on Ser residues in IkappaB-alpha PEST domain. The non-canonical pathway is triggered by particular members of the TNFR superfamily, such as lymphotoxin-beta (LT-beta) or BAFF. It involves NIK and IKK-alpha-mediated p100 phosphorylation and processing to p52, resulting in nuclear translocation of p52/RelB heterodimers.
Class
Environmental Information Processing; Signal transduction
Pathway map
mmu04064  NF-kappa B signaling pathway
mmu04064

Organism
Mus musculus (house mouse) [GN:mmu]
Gene
16818  Lck; lymphocyte protein tyrosine kinase [KO:K05856] [EC:2.7.10.2]
22637  Zap70; zeta-chain (TCR) associated protein kinase [KO:K07360] [EC:2.7.10.2]
16797  Lat; linker for activation of T cells [KO:K07362]
18803  Plcg1; phospholipase C, gamma 1 [KO:K01116] [EC:3.1.4.11]
18761  Prkcq; protein kinase C, theta [KO:K18052] [EC:2.7.11.13]
20963  Syk; spleen tyrosine kinase [KO:K05855] [EC:2.7.10.2]
17096  Lyn; LYN proto-oncogene, Src family tyrosine kinase [KO:K05854] [EC:2.7.10.2]
17060  Blnk; B cell linker [KO:K07371]
12229  Btk; Bruton agammaglobulinemia tyrosine kinase [KO:K07370] [EC:2.7.10.2]
234779  Plcg2; phospholipase C, gamma 2 [KO:K05859] [EC:3.1.4.11]
18751  Prkcb; protein kinase C, beta [KO:K19662] [EC:2.7.11.13]
105844  Card10; caspase recruitment domain family, member 10 [KO:K20912]
108723  Card11; caspase recruitment domain family, member 11 [KO:K07367]
170720  Card14; caspase recruitment domain family, member 14 [KO:K20913]
12042  Bcl10; B cell leukemia/lymphoma 10 [KO:K07368]
240354  Malt1; MALT1 paracaspase [KO:K07369] [EC:3.4.22.-]
16176  Il1b; interleukin 1 beta [KO:K04519]
16177  Il1r1; interleukin 1 receptor, type I [KO:K04386]
17874  Myd88; myeloid differentiation primary response gene 88 [KO:K04729]
16179  Irak1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
266632  Irak4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
22034  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
21926  Tnf; tumor necrosis factor [KO:K03156]
21937  Tnfrsf1a; tumor necrosis factor receptor superfamily, member 1a [KO:K03158]
19766  Ripk1; receptor (TNFRSF)-interacting serine-threonine kinase 1 [KO:K02861] [EC:2.7.11.1]
71609  Tradd; TNFRSF1A-associated via death domain [KO:K03171]
22030  Traf2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
22033  Traf5; TNF receptor-associated factor 5 [KO:K09849]
11797  Birc2; baculoviral IAP repeat-containing 2 [KO:K16060]
11796  Birc3; baculoviral IAP repeat-containing 3 [KO:K16060]
13607  Eda; ectodysplasin-A [KO:K05480]
13608  Edar; ectodysplasin-A receptor [KO:K05162]
171211  Edaradd; EDAR associated via death domain [KO:K23324]
74256  Cyld; CYLD lysine 63 deubiquitinase [KO:K08601] [EC:3.4.19.12]
245527  Eda2r; ectodysplasin A2 receptor [KO:K05163]
230073  Rigi; RNA sensor RIG-I [KO:K12646] [EC:3.6.4.13]
217069  Trim25; tripartite motif-containing 25 [KO:K10652] [EC:2.3.2.27]
16803  Lbp; lipopolysaccharide binding protein [KO:K05399]
12475  Cd14; CD14 antigen [KO:K04391]
21898  Tlr4; toll-like receptor 4 [KO:K10160]
17087  Ly96; lymphocyte antigen 96 [KO:K05400]
117149  Tirap; toll-interleukin 1 receptor (TIR) domain-containing adaptor protein [KO:K05403]
225471  Ticam2; TIR domain containing adaptor molecule 2 [KO:K05409]
106759  Ticam1; TIR domain containing adaptor molecule 1 [KO:K05842]
21947  Cd40lg; CD40 ligand [KO:K03161]
21939  Cd40; CD40 antigen [KO:K03160]
22031  Traf3; TNF receptor-associated factor 3 [KO:K03174]
21943  Tnfsf11; tumor necrosis factor (ligand) superfamily, member 11 [KO:K05473]
21934  Tnfrsf11a; tumor necrosis factor receptor superfamily, member 11a, NFKB activator [KO:K05147]
16992  Lta; lymphotoxin A [KO:K05468]
16994  Ltb; lymphotoxin B [KO:K03157]
50930  Tnfsf14; tumor necrosis factor (ligand) superfamily, member 14 [KO:K05477]
17000  Ltbr; lymphotoxin B receptor [KO:K03159]
53859  Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
26409  Map3k7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
66513  Tab1; TGF-beta activated kinase 1/MAP3K7 binding protein 1 [KO:K04403]
68652  Tab2; TGF-beta activated kinase 1/MAP3K7 binding protein 2 [KO:K04404]
66724  Tab3; TGF-beta activated kinase 1/MAP3K7 binding protein 3 [KO:K12793]
24099  Tnfsf13b; tumor necrosis factor (ligand) superfamily, member 13b [KO:K05476]
72049  Tnfrsf13c; tumor necrosis factor receptor superfamily, member 13c [KO:K05151]
16151  Ikbkg; inhibitor of kappaB kinase gamma [KO:K07210]
12675  Chuk; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
16150  Ikbkb; inhibitor of kappaB kinase beta [KO:K07209] [EC:2.7.11.10]
11545  Parp1; poly (ADP-ribose) polymerase family, member 1 [KO:K24070] [EC:2.4.2.30]
59004  Pias4; protein inhibitor of activated STAT 4 [KO:K16065] [EC:2.3.2.27]
22196  Ube2i; ubiquitin-conjugating enzyme E2I [KO:K10577]
11920  Atm; ataxia telangiectasia mutated [KO:K04728] [EC:2.7.11.1]
57913  Pidd1; p53 induced death domain protein 1 [KO:K10130]
111173  Erc1; ELKS/RAB6-interacting/CAST family member 1 [KO:K16072]
18035  Nfkbia; nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha [KO:K04734]
18033  Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 [KO:K02580]
19697  Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
333654  Ppp1r13l; protein phosphatase 1, regulatory subunit 13 like [KO:K27356]
12633  Cflar; CASP8 and FADD-like apoptosis regulator [KO:K04724]
11798  Xiap; X-linked inhibitor of apoptosis [KO:K04725] [EC:2.3.2.27]
12048  Bcl2l1; BCL2-like 1 [KO:K04570]
12043  Bcl2; B cell leukemia/lymphoma 2 [KO:K02161]
13197  Gadd45a; growth arrest and DNA-damage-inducible 45 alpha [KO:K04402]
17873  Gadd45b; growth arrest and DNA-damage-inducible 45 beta [KO:K04402]
23882  Gadd45g; growth arrest and DNA-damage-inducible 45 gamma [KO:K04402]
22029  Traf1; TNF receptor-associated factor 1 [KO:K03172]
12047  Bcl2a1d; B cell leukemia/lymphoma 2 related protein A1d [KO:K02162]
12044  Bcl2a1a; B cell leukemia/lymphoma 2 related protein A1a [KO:K02162]
12045  Bcl2a1b; B cell leukemia/lymphoma 2 related protein A1b [KO:K02162]
12046  Bcl2a1c; B cell leukemia/lymphoma 2 related protein A1c [KO:K02162]
18034  Nfkb2; nuclear factor of kappa light polypeptide gene enhancer in B cells 2, p49/p100 [KO:K04469]
21929  Tnfaip3; tumor necrosis factor, alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
19225  Ptgs2; prostaglandin-endoperoxide synthase 2 [KO:K11987] [EC:1.14.99.1]
20303  Ccl4; C-C motif chemokine ligand 4 [KO:K12964]
14825  Cxcl1; C-X-C motif chemokine ligand 1 [KO:K05505]
20310  Cxcl2; C-X-C motif chemokine ligand 2 [KO:K05505]
330122  Cxcl3; C-X-C motif chemokine ligand 3 [KO:K05505]
22329  Vcam1; vascular cell adhesion molecule 1 [KO:K06527]
18792  Plau; plasminogen activator, urokinase [KO:K01348] [EC:3.4.21.73]
12995  Csnk2a1; casein kinase 2, alpha 1 polypeptide [KO:K03097] [EC:2.7.11.1]
13000  Csnk2a2; casein kinase 2, alpha prime polypeptide [KO:K03097] [EC:2.7.11.1]
13001  Csnk2b; casein kinase 2, beta polypeptide [KO:K03115]
19698  Relb; avian reticuloendotheliosis viral (v-rel) oncogene related B [KO:K09253]
24047  Ccl19; C-C motif chemokine ligand 19 [KO:K05512]
100862177  Ccl21d; C-C motif chemokine ligand 21D [KO:K16062]
100504346  Ccl21f; C-C motif chemokine ligand 21F [KO:K16062]
100504239  Ccl21e; C-C motif chemokine ligand 21E [KO:K16062]
100042493  Ccl21b; C-C motif chemokine ligand 21B (leucine) [KO:K16062]
18829  Ccl21a; C-C motif chemokine ligand 21 (serine) [KO:K16062]
20315  Cxcl12; C-X-C motif chemokine ligand 12 [KO:K10031]
15894  Icam1; intercellular adhesion molecule 1 [KO:K06490]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C01245  D-myo-Inositol 1,4,5-trisphosphate
Reference
PMID:21772278
  Authors
Oeckinghaus A, Hayden MS, Ghosh S
  Title
Crosstalk in NF-kappaB signaling pathways.
  Journal
Nat Immunol 12:695-708 (2011)
DOI:10.1038/ni.2065
Reference
PMID:19203223
  Authors
Gloire G, Piette J
  Title
Redox regulation of nuclear post-translational modifications during NF-kappaB activation.
  Journal
Antioxid Redox Signal 11:2209-22 (2009)
DOI:10.1089/ARS.2009.2463
Reference
PMID:17183360
  Authors
Perkins ND
  Title
Integrating cell-signalling pathways with NF-kappaB and IKK function.
  Journal
Nat Rev Mol Cell Biol 8:49-62 (2007)
DOI:10.1038/nrm2083
Reference
PMID:16264088
  Authors
Lindstrom TM, Bennett PR
  Title
The role of nuclear factor kappa B in human labour.
  Journal
Reproduction 130:569-81 (2005)
DOI:10.1530/rep.1.00197
Reference
PMID:22017430
  Authors
Razani B, Reichardt AD, Cheng G
  Title
Non-canonical NF-kappaB signaling activation and regulation: principles and perspectives.
  Journal
Immunol Rev 244:44-54 (2011)
DOI:10.1111/j.1600-065X.2011.01059.x
Reference
PMID:21173796
  Authors
Sun SC
  Title
Non-canonical NF-kappaB signaling pathway.
  Journal
Cell Res 21:71-85 (2011)
DOI:10.1038/cr.2010.177
Reference
PMID:17431096
  Authors
Neumann M, Naumann M
  Title
Beyond IkappaBs: alternative regulation of NF-kappaB activity.
  Journal
FASEB J 21:2642-54 (2007)
DOI:10.1096/fj.06-7615rev
Reference
PMID:22119011
  Authors
Verhelst K, Carpentier I, Beyaert R
  Title
Regulation of TNF-induced NF-kappaB activation by different cytoplasmic ubiquitination events.
  Journal
Cytokine Growth Factor Rev 22:277-86 (2011)
DOI:10.1016/j.cytogfr.2011.11.002
Reference
PMID:22017435
  Authors
Rickert RC, Jellusova J, Miletic AV
  Title
Signaling by the tumor necrosis factor receptor superfamily in B-cell biology and disease.
  Journal
Immunol Rev 244:115-33 (2011)
DOI:10.1111/j.1600-065X.2011.01067.x
Reference
PMID:21232019
  Authors
Naude PJ, den Boer JA, Luiten PG, Eisel UL
  Title
Tumor necrosis factor receptor cross-talk.
  Journal
FEBS J 278:888-98 (2011)
DOI:10.1111/j.1742-4658.2011.08017.x
Reference
PMID:16984817
  Authors
Grivennikov SI, Kuprash DV, Liu ZG, Nedospasov SA
  Title
Intracellular signals and events activated by cytokines of the tumor necrosis factor superfamily: From simple paradigms to complex mechanisms.
  Journal
Int Rev Cytol 252:129-61 (2006)
DOI:10.1016/S0074-7696(06)52002-9
Reference
PMID:16356770
  Authors
Wada T, Nakashima T, Hiroshi N, Penninger JM
  Title
RANKL-RANK signaling in osteoclastogenesis and bone disease.
  Journal
Trends Mol Med 12:17-25 (2006)
DOI:10.1016/j.molmed.2005.11.007
Reference
PMID:17098202
  Authors
Schulze-Luehrmann J, Ghosh S
  Title
Antigen-receptor signaling to nuclear factor kappa B.
  Journal
Immunity 25:701-15 (2006)
DOI:10.1016/j.immuni.2006.10.010
Reference
PMID:15134788
  Authors
Weil R, Israel A
  Title
T-cell-receptor- and B-cell-receptor-mediated activation of NF-kappaB in lymphocytes.
  Journal
Curr Opin Immunol 16:374-81 (2004)
DOI:10.1016/j.coi.2004.03.003
Reference
PMID:15905862
  Authors
Siebenlist U, Brown K, Claudio E
  Title
Control of lymphocyte development by nuclear factor-kappaB.
  Journal
Nat Rev Immunol 5:435-45 (2005)
DOI:10.1038/nri1629
Reference
PMID:14657271
  Authors
Lucas PC, McAllister-Lucas LM, Nunez G
  Title
NF-kappaB signaling in lymphocytes: a new cast of characters.
  Journal
J Cell Sci 117:31-9 (2004)
DOI:10.1242/jcs.00904
Reference
PMID:19726767
  Authors
Khan WN
  Title
B cell receptor and BAFF receptor signaling regulation of B cell homeostasis.
  Journal
J Immunol 183:3561-7 (2009)
DOI:10.4049/jimmunol.0800933
Reference
PMID:19302050
  Authors
Vallabhapurapu S, Karin M
  Title
Regulation and function of NF-kappaB transcription factors in the immune system.
  Journal
Annu Rev Immunol 27:693-733 (2009)
DOI:10.1146/annurev.immunol.021908.132641
Reference
PMID:17047224
  Authors
Hacker H, Karin M
  Title
Regulation and function of IKK and IKK-related kinases.
  Journal
Sci STKE 2006:re13 (2006)
DOI:10.1126/stke.3572006re13
Reference
PMID:21872579
  Authors
Sabatel H, Pirlot C, Piette J, Habraken Y
  Title
Importance of PIKKs in NF-kappaB activation by genotoxic stress.
  Journal
Biochem Pharmacol 82:1371-83 (2011)
DOI:10.1016/j.bcp.2011.07.105
Reference
PMID:21187855
  Authors
Miyamoto S
  Title
Nuclear initiated NF-kappaB signaling: NEMO and ATM take center stage.
  Journal
Cell Res 21:116-30 (2011)
DOI:10.1038/cr.2010.179
Reference
PMID:18832076
  Authors
Brzoska K, Szumiel I
  Title
Signalling loops and linear pathways: NF-kappaB activation in response to genotoxic stress.
  Journal
Mutagenesis 24:1-8 (2009)
DOI:10.1093/mutage/gen056
Reference
PMID:17607554
  Authors
Wu ZH, Miyamoto S
  Title
Many faces of NF-kappaB signaling induced by genotoxic stress.
  Journal
J Mol Med (Berl) 85:1187-202 (2007)
DOI:10.1007/s00109-007-0227-9
Reference
PMID:22390971
  Authors
Maelfait J, Beyaert R
  Title
Emerging role of ubiquitination in antiviral RIG-I signaling.
  Journal
Microbiol Mol Biol Rev 76:33-45 (2012)
DOI:10.1128/MMBR.05012-11
Reference
PMID:18613837
  Authors
Ware CF
  Title
Targeting lymphocyte activation through the lymphotoxin and LIGHT pathways.
  Journal
Immunol Rev 223:186-201 (2008)
DOI:10.1111/j.1600-065X.2008.00629.x
Reference
PMID:15546385
  Authors
Schneider K, Potter KG, Ware CF
  Title
Lymphotoxin and LIGHT signaling pathways and target genes.
  Journal
Immunol Rev 202:49-66 (2004)
DOI:10.1111/j.0105-2896.2004.00206.x
Reference
PMID:22152226
  Authors
Remouchamps C, Boutaffala L, Ganeff C, Dejardin E
  Title
Biology and signal transduction pathways of the Lymphotoxin-alphabeta/LTbetaR system.
  Journal
Cytokine Growth Factor Rev 22:301-10 (2011)
DOI:10.1016/j.cytogfr.2011.11.007
Reference
PMID:21135871
  Authors
Liu S, Chen ZJ
  Title
Expanding role of ubiquitination in NF-kappaB signaling.
  Journal
Cell Res 21:6-21 (2011)
DOI:10.1038/cr.2010.170
Reference
PMID:19489733
  Authors
Skaug B, Jiang X, Chen ZJ
  Title
The role of ubiquitin in NF-kappaB regulatory pathways.
  Journal
Annu Rev Biochem 78:769-96 (2009)
DOI:10.1146/annurev.biochem.78.070907.102750
Reference
PMID:20300215
  Authors
Wertz IE, Dixit VM
  Title
Signaling to NF-kappaB: regulation by ubiquitination.
  Journal
Cold Spring Harb Perspect Biol 2:a003350 (2010)
DOI:10.1101/cshperspect.a003350
Reference
PMID:11875461
  Authors
Karin M, Lin A
  Title
NF-kappaB at the crossroads of life and death.
  Journal
Nat Immunol 3:221-7 (2002)
DOI:10.1038/ni0302-221
Reference
PMID:12654254
  Authors
Lin A, Karin M
  Title
NF-kappaB in cancer: a marked target.
  Journal
Semin Cancer Biol 13:107-14 (2003)
DOI:10.1016/S1044-579X(02)00128-1
Reference
PMID:16251197
  Authors
Morlon A, Munnich A, Smahi A
  Title
TAB2, TRAF6 and TAK1 are involved in NF-kappaB activation induced by the TNF-receptor, Edar and its adaptator Edaradd.
  Journal
Hum Mol Genet 14:3751-7 (2005)
DOI:10.1093/hmg/ddi405
Reference
PMID:24070496
  Authors
Sadier A, Viriot L, Pantalacci S, Laudet V
  Title
The ectodysplasin pathway: from diseases to adaptations.
  Journal
Trends Genet 30:24-31 (2014)
DOI:10.1016/j.tig.2013.08.006
Reference
PMID:26260321
  Authors
Verhelst K, Gardam S, Borghi A, Kreike M, Carpentier I, Beyaert R
  Title
XEDAR activates the non-canonical NF-kappaB pathway.
  Journal
Biochem Biophys Res Commun 465:275-80 (2015)
DOI:10.1016/j.bbrc.2015.08.019
Reference
PMID:27508514
  Authors
McDaniel DK, Eden K, Ringel VM, Allen IC
  Title
Emerging Roles for Noncanonical NF-kappaB Signaling in the Modulation of Inflammatory Bowel Disease Pathobiology.
  Journal
Inflamm Bowel Dis 22:2265-79 (2016)
DOI:10.1097/MIB.0000000000000858
Reference
PMID:12787560
  Authors
Mikkola ML, Thesleff I
  Title
Ectodysplasin signaling in development.
  Journal
Cytokine Growth Factor Rev 14:211-24 (2003)
DOI:10.1016/S1359-6101(03)00020-0
Reference
PMID:26646590
  Authors
Hu Y, Ge W, Wang X, Sutendra G, Zhao K, Dedeic Z, Slee EA, Baer C, Lu X
  Title
Caspase cleavage of iASPP potentiates its ability to inhibit p53 and NF-kappaB.
  Journal
Oncotarget 6:42478-90 (2015)
DOI:10.18632/oncotarget.6478
Related
pathway
mmu03050  Proteasome
mmu04020  Calcium signaling pathway
mmu04060  Cytokine-cytokine receptor interaction
mmu04120  Ubiquitin mediated proteolysis
mmu04210  Apoptosis
mmu04380  Osteoclast differentiation
mmu04620  Toll-like receptor signaling pathway
mmu04622  RIG-I-like receptor signaling pathway
mmu04660  T cell receptor signaling pathway
mmu04662  B cell receptor signaling pathway
KO pathway
ko04064   
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