KEGG   PATHWAY: mun04064
Entry
mun04064                    Pathway                                
Name
NF-kappa B signaling pathway - Meriones unguiculatus (Mongolian gerbil)
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
mun04064  NF-kappa B signaling pathway
mun04064

Organism
Meriones unguiculatus (Mongolian gerbil) [GN:mun]
Gene
110548547  Lck; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
110545437  tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
110548013  Lat; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
110552794  Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
110556894  Prkcq; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
110552352  Syk; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
110541812  Lyn; tyrosine-protein kinase Lyn isoform X1 [KO:K05854] [EC:2.7.10.2]
110546295  Blnk; B-cell linker protein [KO:K07371]
110541656  Btk; tyrosine-protein kinase BTK [KO:K07370] [EC:2.7.10.2]
110550263  Plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
110559612  Prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
110558861  Card10; caspase recruitment domain-containing protein 10 isoform X2 [KO:K20912]
110554731  Card11; caspase recruitment domain-containing protein 11 [KO:K07367]
110550037  Card14; caspase recruitment domain-containing protein 14 isoform X2 [KO:K20913]
110558307  Bcl10; B-cell lymphoma/leukemia 10 [KO:K07368]
110546634  Malt1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform X1 [KO:K07369] [EC:3.4.22.-]
110551400  Il1b; interleukin-1 beta [KO:K04519]
110559960  Il1r1; interleukin-1 receptor type 1 isoform X1 [KO:K04386]
110555059  Myd88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
110566945  Irak1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:2.7.11.1]
110563636  Irak4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
110557497  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
110560136  Tnf; LOW QUALITY PROTEIN: tumor necrosis factor [KO:K03156]
110548604  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
110561376  Ripk1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
110545551  Tradd; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
110557003  Traf2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
110566223  Traf5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
110553751  Birc3; baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060]
110553757  Birc2; baculoviral IAP repeat-containing protein 2 isoform X4 [KO:K16060]
110541346  Eda; ectodysplasin-A isoform X1 [KO:K05480]
110564333  Edar; tumor necrosis factor receptor superfamily member EDAR isoform X2 [KO:K05162]
110559767  Edaradd; ectodysplasin-A receptor-associated adapter protein isoform X1 [KO:K23324]
110548860  Cyld; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
110541605  Eda2r; tumor necrosis factor receptor superfamily member 27 isoform X1 [KO:K05163]
110555547  Trim25; E3 ubiquitin/ISG15 ligase TRIM25 isoform X1 [KO:K10652] [EC:2.3.2.27]
110566064  Lbp; lipopolysaccharide-binding protein isoform X1 [KO:K05399]
110557360  Cd14; monocyte differentiation antigen CD14 [KO:K04391]
110565332  Tlr4; toll-like receptor 4 [KO:K10160]
132654750  Ly96; lymphocyte antigen 96 [KO:K05400]
110555283  Tirap; toll/interleukin-1 receptor domain-containing adapter protein [KO:K05403]
110557909  Ticam2; TIR domain-containing adapter molecule 2 [KO:K05409]
110546236  Ticam1; TIR domain-containing adapter molecule 1 [KO:K05842]
110561796  Cd40lg; CD40 ligand [KO:K03161]
110549441  Cd40; tumor necrosis factor receptor superfamily member 5 isoform X1 [KO:K03160]
110553240  Traf3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
110562414  Tnfsf11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
110539357  Tnfrsf11a; tumor necrosis factor receptor superfamily member 11A isoform X1 [KO:K05147]
110560142  Ltb; lymphotoxin-beta [KO:K03157]
110545618  Tnfsf14; tumor necrosis factor ligand superfamily member 14 [KO:K05477]
110548571  Ltbr; tumor necrosis factor receptor superfamily member 3 [KO:K03159]
110545661  Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
110565808  Map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
110557813  Tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
110540621  Tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
110541022  Tab3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X2 [KO:K12793]
110555175  Tnfsf13b; tumor necrosis factor ligand superfamily member 13B isoform X2 [KO:K05476]
110554102  Tnfrsf13c; tumor necrosis factor receptor superfamily member 13C [KO:K05151]
110562528  Ikbkg; NF-kappa-B essential modulator isoform X3 [KO:K07210]
110552966  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
110544653  LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit alpha-like [KO:K04467] [EC:2.7.11.10]
110556613  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
110559482  Parp1; poly [ADP-ribose] polymerase 1 isoform X1 [KO:K24070] [EC:2.4.2.30]
110555610  Pias4; E3 SUMO-protein ligase PIAS4 [KO:K16065] [EC:2.3.2.27]
110548728  Ube2i; SUMO-conjugating enzyme UBC9 [KO:K10577]
110549468  Atm; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
110553932  Pidd1; p53-induced death domain-containing protein 1 [KO:K10130]
110540478  Erc1; ELKS/Rab6-interacting/CAST family member 1 isoform X1 [KO:K16072]
110562401  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
110558602  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X2 [KO:K02580]
110549347  Rela; transcription factor p65 isoform X1 [KO:K04735]
110551500  Ppp1r13l; relA-associated inhibitor [KO:K27356]
110557663  Cflar; CASP8 and FADD-like apoptosis regulator [KO:K04724]
110542115  Xiap; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
110550083  Bcl2l1; bcl-2-like protein 1 isoform X1 [KO:K04570]
110557800  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
110555604  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
110558423  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X2 [KO:K04402]
110559073  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
110563759  Traf1; TNF receptor-associated factor 1 isoform X3 [KO:K03172]
110549489  Bcl2a1; bcl-2-related protein A1 [KO:K02162]
110556458  Nfkb2; nuclear factor NF-kappa-B p100 subunit isoform X1 [KO:K04469]
110566369  Tnfaip3; tumor necrosis factor alpha-induced protein 3 isoform X1 [KO:K11859] [EC:3.4.19.12]
110553489  Ptgs2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
110555685  C-C motif chemokine 4-like [KO:K12964]
110560483  C-X-C motif chemokine 3-like [KO:K05505]
110560489  C-X-C motif chemokine 2 [KO:K05505]
110560490  growth-regulated alpha protein [KO:K05505]
110551868  Vcam1; vascular cell adhesion protein 1 isoform X1 [KO:K06527]
110552013  Plau; urokinase-type plasminogen activator [KO:K01348] [EC:3.4.21.73]
110555818  Csnk2a1; LOW QUALITY PROTEIN: casein kinase II subunit alpha [KO:K03097] [EC:2.7.11.1]
110551175  Csnk2a2; casein kinase II subunit alpha' isoform X1 [KO:K03097] [EC:2.7.11.1]
110560132  Csnk2b; casein kinase II subunit beta [KO:K03115]
110551541  Relb; transcription factor RelB isoform X2 [KO:K09253]
110547116  Ccl19; C-C motif chemokine 19 [KO:K05512]
110547138  Ccl21; C-C motif chemokine 21 [KO:K16062]
110565182  Cxcl12; stromal cell-derived factor 1 isoform X1 [KO:K10031]
110555772  Icam1; intercellular adhesion molecule 1 isoform X1 [KO:K06490]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C01245  D-myo-Inositol 1,4,5-trisphosphate
Reference
  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
  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
  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
  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
  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
  Authors
Sun SC
  Title
Non-canonical NF-kappaB signaling pathway.
  Journal
Cell Res 21:71-85 (2011)
DOI:10.1038/cr.2010.177
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
mun03050  Proteasome
mun04020  Calcium signaling pathway
mun04060  Cytokine-cytokine receptor interaction
mun04120  Ubiquitin mediated proteolysis
mun04210  Apoptosis
mun04380  Osteoclast differentiation
mun04620  Toll-like receptor signaling pathway
mun04622  RIG-I-like receptor signaling pathway
mun04660  T cell receptor signaling pathway
mun04662  B cell receptor signaling pathway
KO pathway
ko04064   
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