KEGG   PATHWAY: mdo04064
Entry
mdo04064                    Pathway                                
Name
NF-kappa B signaling pathway - Monodelphis domestica (gray short-tailed opossum)
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
mdo04064  NF-kappa B signaling pathway
mdo04064

Organism
Monodelphis domestica (gray short-tailed opossum) [GN:mdo]
Gene
100010040  TRB; T-cell receptor beta-2 chain C region [KO:K10785]
100617727  T-cell receptor beta-2 chain C region [KO:K10785]
100025680  LCK; LCK proto-oncogene, Src family tyrosine kinase [KO:K05856] [EC:2.7.10.2]
100025187  ZAP70; tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
103104196  LAT; linker for activation of T-cells [KO:K07362]
100032696  PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
100010321  PRKCQ; protein kinase C theta [KO:K18052] [EC:2.7.11.13]
100015122  uncharacterized LOC100015122 [KO:K06856]
100015499  uncharacterized LOC100015499 [KO:K06856]
100015252  tyrosine-protein phosphatase non-receptor type substrate 1 [KO:K06856]
100015424  uncharacterized LOC100015424 [KO:K06856]
100015641  Ig heavy chain Mem5-like [KO:K06856]
103098203  uncharacterized LOC103098203 [KO:K06856]
100028356  tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
100616821  LYN; LYN proto-oncogene, Src family tyrosine kinase [KO:K05854] [EC:2.7.10.2]
100022658  BLNK; B-cell linker [KO:K07371]
100022891  BTK; Bruton tyrosine kinase [KO:K07370] [EC:2.7.10.2]
100027579  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
100013346  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
100025552  CARD10; caspase recruitment domain family member 10 [KO:K20912]
100012814  CARD11; caspase recruitment domain family member 11 [KO:K07367]
100030808  CARD14; caspase recruitment domain family member 14 [KO:K20913]
100011950  BCL10; B-cell CLL/lymphoma 10 [KO:K07368]
100016169  MALT1; MALT1 paracaspase [KO:K07369] [EC:3.4.22.-]
100026024  IL1B; interleukin 1 beta [KO:K04519]
100017751  IL1R1; interleukin 1 receptor type 1 [KO:K04386]
100029477  IRAK1; interleukin 1 receptor associated kinase 1 [KO:K04730] [EC:2.7.11.1]
100019202  IRAK4; interleukin 1 receptor associated kinase 4 [KO:K04733] [EC:2.7.11.1]
100010055  TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
100023069  TNF; tumor necrosis factor [KO:K03156]
103104450  TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158]
100028597  RIPK1; receptor interacting serine/threonine kinase 1 [KO:K02861] [EC:2.7.11.1]
100019832  TRADD; TNFRSF1A associated via death domain [KO:K03171]
100017243  TRAF2; TNF receptor associated factor 2 [KO:K03173] [EC:2.3.2.27]
100022268  TRAF5; TNF receptor associated factor 5 [KO:K09849]
100010782  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
100010741  baculoviral IAP repeat-containing protein 2-like [KO:K16060]
100014487  EDA; ectodysplasin A [KO:K05480]
100020365  EDAR; ectodysplasin A receptor [KO:K05162]
100617456  EDARADD; EDAR associated death domain [KO:K23324]
100014031  CYLD; CYLD lysine 63 deubiquitinase [KO:K08601] [EC:3.4.19.12]
100026207  EDA2R; ectodysplasin A2 receptor [KO:K05163]
100013883  TRIM25; tripartite motif containing 25 [KO:K10652] [EC:2.3.2.27]
100032863  LBP; lipopolysaccharide-binding protein [KO:K05399]
100026364  CD14; CD14 molecule [KO:K04391]
100014467  TLR4; toll like receptor 4 [KO:K10160]
100027990  LY96; lymphocyte antigen 96 [KO:K05400]
100019477  TIRAP; TIR domain containing adaptor protein [KO:K05403]
100029323  TICAM2; toll like receptor adaptor molecule 2 [KO:K05409]
100023610  TICAM1; toll like receptor adaptor molecule 1 [KO:K05842]
100010217  CD40LG; CD40 ligand [KO:K03161]
100022240  CD40; CD40 molecule [KO:K03160]
100017361  TRAF3; TNF receptor associated factor 3 [KO:K03174]
100011641  TNFSF11; tumor necrosis factor superfamily member 11 [KO:K05473]
100024621  TNFRSF11A; TNF receptor superfamily member 11a [KO:K05147]
100023043  LTA; lymphotoxin alpha [KO:K05468]
100023098  LTB; lymphotoxin beta [KO:K03157]
100026161  TNFSF14; tumor necrosis factor superfamily member 14 [KO:K05477]
100014805  LTBR; lymphotoxin beta receptor [KO:K03159]
100020668  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
100019975  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
100012432  TAB1; TGF-beta activated kinase 1 (MAP3K7) binding protein 1 [KO:K04403]
100026855  TAB2; TGF-beta activated kinase 1/MAP3K7 binding protein 2 [KO:K04404]
100018532  TAB3; TGF-beta activated kinase 1/MAP3K7 binding protein 3 [KO:K12793]
100024583  TNFSF13B; tumor necrosis factor superfamily member 13b [KO:K05476]
100022918  IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
100027952  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
100033031  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
100019495  PARP1; poly(ADP-ribose) polymerase 1 [KO:K24070] [EC:2.4.2.30]
100022245  PIAS4; protein inhibitor of activated STAT 4 [KO:K16065] [EC:2.3.2.27]
100009846  UBE2I; ubiquitin conjugating enzyme E2 I [KO:K10577]
100026797  ATM; ATM serine/threonine kinase [KO:K04728] [EC:2.7.11.1]
100031330  PIDD1; p53-induced death domain protein 1 [KO:K10130]
100017289  ERC1; ELKS/RAB6-interacting/CAST family member 1 [KO:K16072]
100011769  NFKBIA; NFKB inhibitor alpha [KO:K04734]
100014446  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
100030053  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
100010943  PPP1R13L; protein phosphatase 1 regulatory subunit 13 like [KO:K27356]
100617513  CFLAR; CASP8 and FADD like apoptosis regulator [KO:K04724]
100016651  XIAP; X-linked inhibitor of apoptosis [KO:K04725] [EC:2.3.2.27]
100010654  BCL2L1; BCL2 like 1 [KO:K04570]
100016570  BCL2; BCL2, apoptosis regulator [KO:K02161]
100010225  GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
100016952  GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
100014651  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
100015491  TRAF1; TNF receptor associated factor 1 [KO:K03172]
100013805  BCL2A1; BCL2 related protein A1 [KO:K02162]
100029209  NFKB2; nuclear factor kappa B subunit 2 [KO:K04469]
100023722  IL8; interleukin-8 [KO:K10030]
100025842  TNFAIP3; TNF alpha induced protein 3 [KO:K11859] [EC:3.4.19.12]
100024802  PTGS2; prostaglandin-endoperoxide synthase 2 [KO:K11987] [EC:1.14.99.1]
100017283  C-C motif chemokine 4-like [KO:K12964]
100017328  C-C motif chemokine 4-like [KO:K12964]
100017436  C-C motif chemokine 4-like [KO:K12964]
100017364  C-C motif chemokine 4-like [KO:K12964]
100017393  C-C motif chemokine 4-like [KO:K12964]
103099606  C-C motif chemokine 3-like [KO:K12964]
103101444  C-C motif chemokine 4-like [KO:K12964]
100020842  C-C motif chemokine 4-like [KO:K12964]
100023783  CXCL1; growth-regulated alpha protein [KO:K05505]
100032965  VCAM1; vascular cell adhesion molecule 1 [KO:K06527]
100617123  PLAU; plasminogen activator, urokinase [KO:K01348] [EC:3.4.21.73]
100025237  CSNK2A2; casein kinase 2 alpha 2 [KO:K03097] [EC:2.7.11.1]
100011177  CSNK2A1; casein kinase 2 alpha 1 [KO:K03097] [EC:2.7.11.1]
100025065  CSNK2B; casein kinase 2 beta [KO:K03115]
100618518  RELB; RELB proto-oncogene, NF-kB subunit [KO:K09253]
100028745  CCL19; C-C motif chemokine ligand 19 [KO:K05512]
100028728  CCL21; C-C motif chemokine ligand 21 [KO:K16062]
100016207  CXCL12; C-X-C motif chemokine ligand 12 [KO:K10031]
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
mdo03050  Proteasome
mdo04020  Calcium signaling pathway
mdo04060  Cytokine-cytokine receptor interaction
mdo04120  Ubiquitin mediated proteolysis
mdo04210  Apoptosis
mdo04380  Osteoclast differentiation
mdo04620  Toll-like receptor signaling pathway
mdo04622  RIG-I-like receptor signaling pathway
mdo04660  T cell receptor signaling pathway
mdo04662  B cell receptor signaling pathway
KO pathway
ko04064   
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