KEGG   PATHWAY: mpah04668
Entry
mpah04668                   Pathway                                
Name
TNF signaling pathway - Mus pahari (shrew 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
mpah04668  TNF signaling pathway
mpah04668

Other DBs
GO: 0033209
Organism
Mus pahari (shrew mouse) [GN:mpah]
Gene
110312759  Pgam5; serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X1 [KO:K15637] [EC:3.1.3.16]
110313464  Ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
110313538  Xiap; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
110313859  Tab3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
110313900  Vegfd; vascular endothelial growth factor D isoform X1 [KO:K05449]
110315297  [KO:K11987] [EC:1.14.99.1]
110315994  Creb5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
110316152  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
110316225  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
110317041  Rela; transcription factor p65 [KO:K04735]
110317140  Il6; interleukin-6 [KO:K05405]
110317258  Akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110317574  Jag1; protein jagged-1 [KO:K06052]
110317579  Itch; E3 ubiquitin-protein ligase Itchy homolog [KO:K05632] [EC:2.3.2.26]
110317821  Atf2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
110318332  Mmp9; matrix metalloproteinase-9 isoform X1 [KO:K01403] [EC:3.4.24.35]
110318364  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
110318405  Traf2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
110318878  Cebpb; CCAAT/enhancer-binding protein beta [KO:K10048]
110319269  Dab2ip; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
110319321  Il1b; interleukin-1 beta isoform X1 [KO:K04519]
110319363  Traf1; TNF receptor-associated factor 1 [KO:K03172]
110319750  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110319789  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
110319965  Vcam1; vascular cell adhesion protein 1 isoform X1 [KO:K06527]
110320020  Mapk3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
110320052  Csf1; macrophage colony-stimulating factor 1 [KO:K05453]
110320678  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
110321554  Ptgs2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
110321675  Casp8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
110321877  [KO:K16060]
110321922  Cflar; CASP8 and FADD-like apoptosis regulator [KO:K04724]
110322137  Traf5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
110322284  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110322391  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
110322439  Il18r1; interleukin-18 receptor 1 isoform X1 [KO:K05173]
110322462  Ccl20; C-C motif chemokine 20 isoform X1 [KO:K14625]
110322592  Sele; E-selectin [KO:K06494]
110322748  Frmd8; FERM domain-containing protein 8 [KO:K23972]
110322865  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
110323252  Jun; transcription factor AP-1 [KO:K04448]
110323346  Ifnb1; interferon beta [KO:K05415]
110323448  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110323744  Tnfrsf1b; tumor necrosis factor receptor superfamily member 1B [KO:K05141]
110324254  Rps6ka5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
110324365  Fos; proto-oncogene c-Fos isoform X1 [KO:K04379]
110324376  Adam17; disintegrin and metalloproteinase domain-containing protein 17 isoform X1 [KO:K06059] [EC:3.4.24.86]
110324386  Akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110324484  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
110324559  Traf3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
110325048  Mmp14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
110325466  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
110325658  Ripk3; receptor-interacting serine/threonine-protein kinase 3 isoform X1 [KO:K08847] [EC:2.7.11.1]
110326077  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
110327244  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
110327251  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110327515  Icam1; intercellular adhesion molecule 1 [KO:K06490]
110327576  [KO:K16060]
110327820  [KO:K01394] [EC:3.4.24.17]
110328081  [KO:K16060]
110328167  Casp7; caspase-7 [KO:K04397] [EC:3.4.22.60]
110328811  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
110329343  Mapk1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
110329377  Dnm1l; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
110330449  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
110330675  Cxcl10; C-X-C motif chemokine 10 [KO:K12671]
110330793  Lif; leukemia inhibitory factor isoform X1 [KO:K05419]
110330904  [KO:K05505]
110330924  [KO:K05505]
110330950  [KO:K05505]
110331003  Cxcl6; C-X-C motif chemokine 6 [KO:K05506]
110331197  Map2k3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
110331335  Map2k6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
110331382  Rhbdf1; inactive rhomboid protein 1 isoform X1 [KO:K27588]
110331563  Map2k4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
110331924  [KO:K14624]
110332048  Irf1; interferon regulatory factor 1 isoform X1 [KO:K09444]
110332110  Rhbdf2; inactive rhomboid protein 2 isoform X1 [KO:K27588]
110332146  Socs3; suppressor of cytokine signaling 3 [KO:K04696]
110332218  Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
110332438  Csf2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
110332475  [KO:K14624]
110332476  Ccl5; C-C motif chemokine 5 [KO:K12499]
110332581  [KO:K17072]
110332652  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
110332797  Fas; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
110333124  Fadd; FAS-associated death domain protein [KO:K02373]
110333248  Map3k8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
110333762  Ripk1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
110334180  Edn1; endothelin-1 [KO:K16366]
110334495  Mapk11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
110334538  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
110334651  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
110334829  Mapk12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
110334874  Tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
110335526  Atf6b; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
110335791  Tnf; tumor necrosis factor isoform X1 [KO:K03156]
110335951  Lta; lymphotoxin-alpha [KO:K05468]
110336182  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
110336400  Map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
110336420  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
110336603  Bag4; BAG family molecular chaperone regulator 4 isoform X1 [KO:K09558]
110336608  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
110336732  Vegfc; vascular endothelial growth factor C [KO:K05449]
110337049  Bcl3; B-cell lymphoma 3 protein [KO:K09258]
110337507  Cyld; ubiquitin carboxyl-terminal hydrolase CYLD [KO:K08601] [EC:3.4.19.12]
110337565  Junb; transcription factor jun-B [KO:K09028]
110337608  Tradd; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
110337621  Cx3cl1; fractalkine [KO:K05508]
110337630  Il15; interleukin-15 isoform X1 [KO:K05433]
110337641  Nod2; nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165]
110337670  Mlkl; mixed lineage kinase domain-like protein isoform X1 [KO:K08849] [EC:2.7.11.1]
110337870  Map3k5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
110337896  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
110337946  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
110338176  Tab2; LOW QUALITY PROTEIN: TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
110338221  Tnfaip3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
110338656  Map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
110338975  Creb3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
110339061  Rps6ka4; ribosomal protein S6 kinase alpha-4 isoform X1 [KO:K16510] [EC:2.7.11.1]
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
mpah04010  MAPK signaling pathway
mpah04064  NF-kappa B signaling pathway
mpah04120  Ubiquitin mediated proteolysis
mpah04151  PI3K-Akt signaling pathway
mpah04210  Apoptosis
KO pathway
ko04668   

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