KEGG   PATHWAY: mun04668
Entry
mun04668                    Pathway                                
Name
TNF signaling pathway - Meriones unguiculatus (Mongolian gerbil)
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
mun04668  TNF signaling pathway
mun04668

Other DBs
GO: 0033209
Organism
Meriones unguiculatus (Mongolian gerbil) [GN:mun]
Gene
110539385  Vegfd; vascular endothelial growth factor D isoform X3 [KO:K05449]
110539463  Il6; interleukin-6 [KO:K05405]
110540621  Tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
110540824  Bag4; BAG family molecular chaperone regulator 4 isoform X1 [KO:K09558]
110541022  Tab3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X2 [KO:K12793]
110541303  Ifnb1; interferon beta [KO:K05415]
110542115  Xiap; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
110542126  Vegfc; vascular endothelial growth factor C [KO:K05449]
110542259  Rhbdf2; inactive rhomboid protein 2 isoform X1 [KO:K27588]
110544244  Edn1; endothelin-1 [KO:K16366]
110544653  [KO:K04467] [EC:2.7.11.10]
110545113  Casp7; caspase-7 isoform X2 [KO:K04397] [EC:3.4.22.60]
110545505  Csf1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453]
110545551  Tradd; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
110545661  Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
110545861  Junb; transcription factor JunB [KO:K09028]
110546008  Mlkl; mixed lineage kinase domain-like protein isoform X1 [KO:K08849] [EC:2.7.11.1]
110546562  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
110546585  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
110546885  Fadd; FAS-associated death domain protein [KO:K02373]
110546962  Fos; protein c-Fos [KO:K04379]
110547978  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
110548394  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110548604  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
110548762  Irf1; interferon regulatory factor 1 isoform X1 [KO:K09444]
110548860  Cyld; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
110548935  Cebpb; CCAAT/enhancer-binding protein beta [KO:K10048]
110549145  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
110549233  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
110549307  Mmp9; matrix metalloproteinase-9 isoform X1 [KO:K01403] [EC:3.4.24.35]
110549339  Frmd8; FERM domain-containing protein 8 isoform X1 [KO:K23972]
110549347  Rela; transcription factor p65 isoform X1 [KO:K04735]
110549673  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
110549680  Mapk11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
110549859  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
110549934  Sele; E-selectin [KO:K06494]
110550039  Mmp14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
110550317  Socs3; suppressor of cytokine signaling 3 [KO:K04696]
110550572  Itch; E3 ubiquitin-protein ligase Itchy homolog isoform X1 [KO:K05632] [EC:2.3.2.26]
110551039  [KO:K17072]
110551400  Il1b; interleukin-1 beta [KO:K04519]
110551437  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
110551515  Bcl3; B-cell lymphoma 3 protein [KO:K09258]
110551593  Rps6ka4; ribosomal protein S6 kinase alpha-4 isoform X1 [KO:K16510] [EC:2.7.11.1]
110551868  Vcam1; vascular cell adhesion protein 1 isoform X1 [KO:K06527]
110552225  Map2k4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
110552285  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
110552966  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
110553170  Pgam5; serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X1 [KO:K15637] [EC:3.1.3.16]
110553240  Traf3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
110553489  Ptgs2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
110553683  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
110553751  Birc3; baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060]
110553757  Birc2; baculoviral IAP repeat-containing protein 2 isoform X4 [KO:K16060]
110553796  Mapk1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
110554250  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
110554628  Map3k5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
110554970  Creb5; cyclic AMP-responsive element-binding protein 5 isoform X2 [KO:K09047]
110555614  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
110555684  Ccl5; C-C motif chemokine 5 [KO:K12499]
110555750  Tnfrsf1b; tumor necrosis factor receptor superfamily member 1B isoform X1 [KO:K05141]
110555772  Icam1; intercellular adhesion molecule 1 isoform X1 [KO:K06490]
110556239  Cxcl10; C-X-C motif chemokine 10 [KO:K12671]
110556252  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
110556511  Ripk3; receptor-interacting serine/threonine-protein kinase 3 isoform X1 [KO:K08847] [EC:2.7.11.1]
110556579  Atf2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
110556613  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
110556719  Akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110557003  Traf2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
110557386  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
110557662  Casp8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
110557663  Cflar; CASP8 and FADD-like apoptosis regulator [KO:K04724]
110557813  Tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
110557820  Lif; leukemia inhibitory factor isoform X1 [KO:K05419]
110558090  [KO:K01394] [EC:3.4.24.17]
110558401  Map3k8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
110558602  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X2 [KO:K02580]
110558966  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110559000  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
110559526  Cx3cl1; fractalkine [KO:K05508]
110559727  Jun; transcription factor Jun [KO:K04448]
110560136  Tnf; LOW QUALITY PROTEIN: tumor necrosis factor [KO:K03156]
110560337  Dab2ip; disabled homolog 2-interacting protein isoform X9 [KO:K19901]
110560483  [KO:K05505]
110560486  [KO:K05506]
110560489  [KO:K05505]
110560490  [KO:K05505]
110560783  Nod2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165]
110561254  Ccl20; C-C motif chemokine 20 isoform X1 [KO:K14625]
110561270  Rhbdf1; inactive rhomboid protein 1 isoform X1 [KO:K27588]
110561376  Ripk1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
110561521  Fas; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
110561677  Map2k3; dual specificity mitogen-activated protein kinase kinase 3 isoform X2 [KO:K04432] [EC:2.7.12.2]
110561713  Csf2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
110561882  Creb3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
110562067  Dnm1l; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
110562401  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
110562528  Ikbkg; NF-kappa-B essential modulator isoform X3 [KO:K07210]
110562738  Il15; interleukin-15 isoform X1 [KO:K05433]
110562875  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
110563015  Map2k6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
110563512  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
110563759  Traf1; TNF receptor-associated factor 1 isoform X3 [KO:K03172]
110564190  Adam17; disintegrin and metalloproteinase domain-containing protein 17 isoform X1 [KO:K06059] [EC:3.4.24.86]
110564325  Rps6ka5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
110564365  [KO:K14624]
110564504  Il18r1; interleukin-18 receptor 1 isoform X1 [KO:K05173]
110564629  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
110564898  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110565112  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110565314  Jag1; protein jagged-1 [KO:K06052]
110565383  Atf6b; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
110565808  Map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
110566223  Traf5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
110566369  Tnfaip3; tumor necrosis factor alpha-induced protein 3 isoform X1 [KO:K11859] [EC:3.4.19.12]
132650544  Map2k7; LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
132653623  Casp3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
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
mun04010  MAPK signaling pathway
mun04064  NF-kappa B signaling pathway
mun04120  Ubiquitin mediated proteolysis
mun04151  PI3K-Akt signaling pathway
mun04210  Apoptosis
KO pathway
ko04668   

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