KEGG   PATHWAY: mcoc04668
Entry
mcoc04668                   Pathway                                
Name
TNF signaling pathway - Mastomys coucha (southern multimammate mouse)
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
mcoc04668  TNF signaling pathway
mcoc04668

Other DBs
GO: 0033209
Organism
Mastomys coucha (southern multimammate mouse) [GN:mcoc]
Gene
116067982  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
116068121  Pgam5; serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X1 [KO:K15637] [EC:3.1.3.16]
116068848  Map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
116068881  Lif; leukemia inhibitory factor isoform X1 [KO:K05419]
116069008  Traf5; TNF receptor-associated factor 5 [KO:K09849]
116069014  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
116069066  Bag4; BAG family molecular chaperone regulator 4 isoform X1 [KO:K09558]
116069240  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
116069284  Vegfc; vascular endothelial growth factor C [KO:K05449]
116069491  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
116069657  Il15; interleukin-15 isoform X1 [KO:K05433]
116069739  Junb; transcription factor jun-B [KO:K09028]
116069823  Nod2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165]
116069824  Cyld; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
116069910  Cx3cl1; fractalkine [KO:K05508]
116070032  Tradd; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
116070196  Mlkl; mixed lineage kinase domain-like protein [KO:K08849] [EC:2.7.11.1]
116070506  Ptgs2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
116070638  [KO:K05506]
116070642  [KO:K05505]
116070643  [KO:K05505]
116070644  [KO:K05505]
116070836  Sele; E-selectin [KO:K06494]
116072442  [KO:K01394] [EC:3.4.24.17]
116072766  [KO:K16060]
116072810  [KO:K16060]
116073076  Icam1; intercellular adhesion molecule 1 [KO:K06490]
116073648  Mapk6; mitogen-activated protein kinase 6 [KO:K04371] [EC:2.7.11.24]
116073764  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
116073929  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116074547  Tnf; tumor necrosis factor isoform X1 [KO:K03156]
116074778  Lta; lymphotoxin-alpha [KO:K05468]
116075007  Atf6b; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
116075101  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
116075516  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
116076094  Tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
116076129  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
116076210  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
116076765  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
116076945  Csf2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
116076990  [KO:K14624]
116077650  Ccl5; C-C motif chemokine 5 [KO:K12499]
116077717  Rhbdf2; inactive rhomboid protein 2 isoform X1 [KO:K27588]
116077765  Mapk11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
116077791  Mapk12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
116077938  Map2k3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
116077958  [KO:K14624]
116078119  Rhbdf1; inactive rhomboid protein 1 [KO:K27588]
116078253  Irf1; interferon regulatory factor 1 [KO:K09444]
116078408  Socs3; suppressor of cytokine signaling 3 [KO:K04696]
116078795  [KO:K17072]
116079018  Map2k4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
116079101  Xiap; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
116079135  Map2k6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
116079161  Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
116079779  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116080005  Rps6ka5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
116080443  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
116080518  Fos; proto-oncogene c-Fos [KO:K04379]
116080944  Traf3; TNF receptor-associated factor 3 [KO:K03174]
116080989  Adam17; disintegrin and metalloproteinase domain-containing protein 17 [KO:K06059] [EC:3.4.24.86]
116081785  Edn1; endothelin-1 [KO:K16366]
116082569  Ripk1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
116083721  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
116084409  Ripk3; receptor-interacting serine/threonine-protein kinase 3 [KO:K08847] [EC:2.7.11.1]
116084514  Mmp14; matrix metalloproteinase-14 isoform X1 [KO:K07763] [EC:3.4.24.80]
116085336  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
116085631  Dnm1l; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
116085641  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116086280  Ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
116086620  Tab3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
116086796  Map3k8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
116088003  Map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
116088350  Il18r1; interleukin-18 receptor 1 isoform X1 [KO:K05173]
116088466  Cflar; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
116088467  Casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
116088513  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
116089260  Ccl20; C-C motif chemokine 20 [KO:K14625]
116089826  Traf2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
116090053  Traf1; TNF receptor-associated factor 1 [KO:K03172]
116090069  Dab2ip; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
116090438  Vegfd; vascular endothelial growth factor D isoform X1 [KO:K05449]
116090490  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
116090916  Il1b; interleukin-1 beta [KO:K04519]
116091010  Jag1; protein jagged-1 [KO:K06052]
116091228  Itch; E3 ubiquitin-protein ligase Itchy homolog [KO:K05632] [EC:2.3.2.26]
116091432  Cebpb; CCAAT/enhancer-binding protein beta [KO:K10048]
116091666  Atf2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
116092533  Mmp9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
116093212  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
116093601  Csf1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453]
116093675  Vcam1; vascular cell adhesion protein 1 [KO:K06527]
116093825  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
116095058  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116095400  Ifnb1; interferon beta [KO:K05415]
116095903  Creb3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
116096245  Jun; transcription factor AP-1 [KO:K04448]
116096465  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
116096996  Tnfrsf1b; tumor necrosis factor receptor superfamily member 1B isoform X1 [KO:K05141]
116097037  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116097436  Il6; interleukin-6 [KO:K05405]
116097745  Tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
116097806  Tnfaip3; tumor necrosis factor alpha-induced protein 3 isoform X1 [KO:K11859] [EC:3.4.19.12]
116097922  Map3k5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
116098735  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
116098936  Creb5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
116099614  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
116101774  Bcl3; B-cell lymphoma 3 protein [KO:K09258]
116101889  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116102969  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
116103283  Fadd; FAS-associated death domain protein [KO:K02373]
116103403  Rela; transcription factor p65 isoform X1 [KO:K04735]
116103418  Frmd8; FERM domain-containing protein 8 isoform X1 [KO:K23972]
116103460  Rps6ka4; ribosomal protein S6 kinase alpha-4 isoform X1 [KO:K16510] [EC:2.7.11.1]
116103761  Fas; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
116103881  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
116104023  Casp7; caspase-7 [KO:K04397] [EC:3.4.22.60]
116104026  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116104497  Cxcl10; C-X-C motif chemokine 10 [KO:K12671]
116104574  [KO:K04397] [EC:3.4.22.60]
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
mcoc04010  MAPK signaling pathway
mcoc04064  NF-kappa B signaling pathway
mcoc04120  Ubiquitin mediated proteolysis
mcoc04151  PI3K-Akt signaling pathway
mcoc04210  Apoptosis
KO pathway
ko04668   

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