KEGG   PATHWAY: anu04668
Entry
anu04668                    Pathway                                
Name
TNF signaling pathway - Arvicanthis niloticus (African grass rat)
Description
Tumor necrosis factor (TNF), as a critical cytokine, can induce a wide range of intracellular signal pathways including apoptosis and cell survival as well as inflammation and immunity. Activated TNF is assembled to a homotrimer and binds to its receptors (TNFR1, TNFR2) resulting in the trimerization of TNFR1 or TNFR2. TNFR1 is expressed by nearly all cells and is the major receptor for TNF (also called TNF-alpha). In contrast, TNFR2 is expressed in limited cells such as CD4 and CD8 T lymphocytes, endothelial cells, microglia, oligodendrocytes, neuron subtypes, cardiac myocytes, thymocytes and human mesenchymal stem cells. It is the receptor for both TNF and LTA (also called TNF-beta). Upon binding of the ligand, TNFR mediates the association of some adaptor proteins such as TRADD or TRAF2, which in turn initiate recruitment of signal transducers. TNFR1 signaling induces activation of many genes, primarily controlled by two distinct pathways, NF-kappa B pathway and the MAPK cascade, or apoptosis and necroptosis. TNFR2 signaling activates NF-kappa B pathway including PI3K-dependent NF-kappa B pathway and JNK pathway leading to survival.
Class
Environmental Information Processing; Signal transduction
Pathway map
anu04668  TNF signaling pathway
anu04668

Other DBs
GO: 0033209
Organism
Arvicanthis niloticus (African grass rat) [GN:anu]
Gene
117724681  Tnf; tumor necrosis factor isoform X1 [KO:K03156]
117714946  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
117721559  Bag4; BAG family molecular chaperone regulator 4 isoform X1 [KO:K09558]
117716809  Adam17; disintegrin and metalloproteinase domain-containing protein 17 isoform X1 [KO:K06059] [EC:3.4.24.86]
117710668  Rhbdf1; inactive rhomboid protein 1 [KO:K27588]
117711858  Rhbdf2; inactive rhomboid protein 2 [KO:K27588]
117712432  Frmd8; FERM domain-containing protein 8 isoform X1 [KO:K23972]
117723297  Tradd; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
117710914  Traf2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
117716371  Traf5; TNF receptor-associated factor 5 [KO:K09849]
117713706  Ripk1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
117699887  baculoviral IAP repeat-containing protein 2 [KO:K16060]
117699964  baculoviral IAP repeat-containing protein 3 [KO:K16060]
117698575  Map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
117719404  Tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
117700141  Tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
117694849  Tab3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
117710639  Map2k4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
117697775  Map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
117705037  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
117709966  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
117709069  Jun; transcription factor AP-1 [KO:K04448]
117697448  Fos; proto-oncogene c-Fos [KO:K04379]
117704516  Itch; E3 ubiquitin-protein ligase Itchy homolog [KO:K05632] [EC:2.3.2.26]
117705809  Cflar; CASP8 and FADD-like apoptosis regulator [KO:K04724]
117710465  Map2k3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
117710811  Map2k6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
117724304  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
117724423  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
117718601  Mapk12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
117718602  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
117702681  Cebpb; CCAAT/enhancer-binding protein beta [KO:K10048]
117701010  Map3k5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
117711275  Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
117695513  Ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
117721547  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
117701914  inhibitor of nuclear factor kappa-B kinase subunit alpha-like [KO:K04467] [EC:2.7.11.10]
117712831  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
117717335  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
117722582  Rela; transcription factor p65 [KO:K04735]
117707042  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
117714402  Map3k8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
117699009  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
117717711  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
117693439  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
117697424  Rps6ka5; ribosomal protein S6 kinase alpha-5 [KO:K04445] [EC:2.7.11.1]
117711631  Rps6ka4; ribosomal protein S6 kinase alpha-4 isoform X1 [KO:K16510] [EC:2.7.11.1]
117705049  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
117704442  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
117707799  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
117709015  Creb3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
117720532  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
117696466  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
117703314  Atf2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
117719125  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
117720600  Creb5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
117724754  Atf6b; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
117705541  Ripk3; receptor-interacting serine/threonine-protein kinase 3 [KO:K08847] [EC:2.7.11.1]
117710030  Fadd; FAS-associated death domain protein [KO:K02373]
117704983  Casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
117696275  Casp7; caspase-7 [KO:K04397] [EC:3.4.22.60]
117721984  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
117723256  Mlkl; mixed lineage kinase domain-like protein [KO:K08849] [EC:2.7.11.1]
117698034  Pgam5; serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X1 [KO:K15637] [EC:3.1.3.16]
117717873  Dnm1l; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
117722957  Cyld; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
117694154  Xiap; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
117711484  C-C motif chemokine 12-like [KO:K14624]
117709856  C-C motif chemokine 2 [KO:K14624]
117711280  Ccl5; C-C motif chemokine 5 [KO:K12499]
117722742  Ccl20; LOW QUALITY PROTEIN: C-C motif chemokine 20 [KO:K14625]
117712876  growth-regulated alpha protein isoform X1 [KO:K05505]
117712987  C-X-C motif chemokine 2 [KO:K05505]
117713027  C-X-C motif chemokine 3 [KO:K05505]
117712853  C-X-C motif chemokine 5-like [KO:K05506]
117699623  Cxcl10; C-X-C motif chemokine 10 [KO:K12671]
117723397  Cx3cl1; fractalkine [KO:K05508]
117706885  Csf1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453]
117711918  Csf2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
117700780  Fas; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
117722575  Il18r1; interleukin-18 receptor 1 isoform X1 [KO:K05173]
117703754  Jag1; protein jagged-1 [KO:K06052]
117704054  Il1b; interleukin-1 beta isoform X1 [KO:K04519]
117720807  Il6; interleukin-6 [KO:K05405]
117723173  Il15; interleukin-15 isoform X1 [KO:K05433]
117712964  Lif; leukemia inhibitory factor [KO:K05419]
117724852  Lta; lymphotoxin-alpha [KO:K05468]
117698122  Bcl3; B-cell lymphoma 3 protein [KO:K09258]
117711957  Socs3; suppressor of cytokine signaling 3 [KO:K04696]
117701024  Tnfaip3; tumor necrosis factor alpha-induced protein 3 isoform X1 [KO:K11859] [EC:3.4.19.12]
117703605  Traf1; TNF receptor-associated factor 1 [KO:K03172]
117711563  T-cell-specific guanine nucleotide triphosphate-binding protein 2-like [KO:K17072]
117710334  T-cell-specific guanine nucleotide triphosphate-binding protein 2-like [KO:K17072]
117711020  T-cell-specific guanine nucleotide triphosphate-binding protein 2-like [KO:K17072]
117723419  Junb; transcription factor jun-B [KO:K09028]
117699631  stromelysin-1 [KO:K01394] [EC:3.4.24.17]
117704142  Mmp9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
117705214  Mmp14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
117713961  Edn1; endothelin-1 [KO:K16366]
117695345  Vegfd; vascular endothelial growth factor D isoform X1 [KO:K05449]
117721236  Vegfc; vascular endothelial growth factor C [KO:K05449]
117723222  Nod2; nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165]
117714210  Icam1; intercellular adhesion molecule 1 [KO:K06490]
117716481  Sele; E-selectin [KO:K06494]
117716615  E-selectin-like [KO:K06494]
117707792  Vcam1; vascular cell adhesion protein 1 [KO:K06527]
117716475  Ptgs2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
117709653  Tnfrsf1b; tumor necrosis factor receptor superfamily member 1B isoform X1 [KO:K05141]
117697234  Traf3; TNF receptor-associated factor 3 [KO:K03174]
117706649  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
117693421  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
117708986  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
117721973  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
117723761  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
117708961  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
117697536  Akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
117706636  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
117721481  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
117703388  Dab2ip; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
117709821  Irf1; interferon regulatory factor 1 [KO:K09444]
117709633  Ifnb1; interferon beta [KO:K05415]
Reference
  Authors
Chu WM
  Title
Tumor necrosis factor.
  Journal
Cancer Lett 328:222-5 (2013)
DOI:10.1016/j.canlet.2012.10.014
Reference
  Authors
Shuh M, Bohorquez H, Loss GE Jr, Cohen AJ
  Title
Tumor Necrosis Factor-alpha: Life and Death of Hepatocytes During Liver Ischemia/Reperfusion Injury.
  Journal
Ochsner J 13:119-30 (2013)
Reference
  Authors
MacEwan DJ
  Title
TNF receptor subtype signalling: differences and cellular consequences.
  Journal
Cell Signal 14:477-92 (2002)
DOI:10.1016/S0898-6568(01)00262-5
Reference
  Authors
Newton K, Dixit VM
  Title
Signaling in innate immunity and inflammation.
  Journal
Cold Spring Harb Perspect Biol 4:a006049 (2012)
DOI:10.1101/cshperspect.a006049
Reference
  Authors
Pomerantz JL, Baltimore D
  Title
NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase.
  Journal
EMBO J 18:6694-704 (1999)
DOI:10.1093/emboj/18.23.6694
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
Faustman D, Davis M
  Title
TNF receptor 2 pathway: drug target for autoimmune diseases.
  Journal
Nat Rev Drug Discov 9:482-93 (2010)
DOI:10.1038/nrd3030
Reference
  Authors
Chan FK, Shisler J, Bixby JG, Felices M, Zheng L, Appel M, Orenstein J, Moss B, Lenardo MJ
  Title
A role for tumor necrosis factor receptor-2 and receptor-interacting protein in programmed necrosis and antiviral responses.
  Journal
J Biol Chem 278:51613-21 (2003)
DOI:10.1074/jbc.M305633200
Reference
  Authors
Lee MY, Nam KH, Choi KC
  Title
iRhoms; Its Functions and Essential Roles.
  Journal
Biomol Ther (Seoul) 24:109-14 (2016)
DOI:10.4062/biomolther.2015.149
Related
pathway
anu04010  MAPK signaling pathway
anu04064  NF-kappa B signaling pathway
anu04120  Ubiquitin mediated proteolysis
anu04151  PI3K-Akt signaling pathway
anu04210  Apoptosis
KO pathway
ko04668   
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