KEGG   PATHWAY: tup04668
Entry
tup04668                    Pathway                                
Name
TNF signaling pathway - Tupaia chinensis (Chinese tree shrew)
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
tup04668  TNF signaling pathway
tup04668

Other DBs
GO: 0033209
Organism
Tupaia chinensis (Chinese tree shrew) [GN:tup]
Gene
102467686  [KO:K05505]
102467954  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
102468245  [KO:K09048]
102468813  MMP14; matrix metallopeptidase 14 [KO:K07763] [EC:3.4.24.80]
102468817  JUNB; JunB proto-oncogene, AP-1 transcription factor subunit [KO:K09028]
102469074  CREB3; cAMP responsive element binding protein 3 [KO:K09048]
102469401  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
102469956  RHBDF2; rhomboid 5 homolog 2 [KO:K27588]
102470949  CASP7; caspase 7 [KO:K04397] [EC:3.4.22.60]
102471426  MLKL; mixed lineage kinase domain like pseudokinase [KO:K08849] [EC:2.7.11.1]
102471499  TRAF3; TNF receptor associated factor 3 [KO:K03174]
102471631  TNFRSF1B; TNF receptor superfamily member 1B [KO:K05141]
102471928  CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048]
102472172  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102472233  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
102472622  [KO:K05505]
102472926  CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
102473097  PGAM5; PGAM family member 5, mitochondrial serine/threonine protein phosphatase [KO:K15637] [EC:3.1.3.16]
102473406  ATF2; activating transcription factor 2 [KO:K04450]
102473925  C8G; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
102474297  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102475138  IL1B; interleukin 1 beta [KO:K04519]
102475703  EDN1; endothelin 1 [KO:K16366]
102475730  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
102476422  IL15; interleukin 15 [KO:K05433]
102476496  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102476587  FAS; Fas cell surface death receptor [KO:K04390]
102476608  JAG1; jagged 1 [KO:K06052]
102476758  IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
102477224  TNFAIP3; TNF alpha induced protein 3 [KO:K11859] [EC:3.4.19.12]
102477331  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
102477501  BCL3; B-cell CLL/lymphoma 3 [KO:K09258]
102478124  TRAF5; TNF receptor associated factor 5 [KO:K09849]
102478154  ATF4; activating transcription factor 4 [KO:K04374]
102478264  PTGS2; prostaglandin-endoperoxide synthase 2 [KO:K11987] [EC:1.14.99.1]
102478593  IL18R1; interleukin 18 receptor 1 [KO:K05173]
102478636  TRADD; TNFRSF1A associated via death domain [KO:K03171]
102478674  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
102479566  TAB1; TGF-beta activated kinase 1 (MAP3K7) binding protein 1 [KO:K04403]
102479844  DAB2IP; DAB2 interacting protein [KO:K19901]
102481241  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
102481282  CCL5; C-C motif chemokine ligand 5 [KO:K12499]
102482054  MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
102483057  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102483329  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102484080  ATF6B; activating transcription factor 6 beta [KO:K09049]
102484102  CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048]
102484444  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
102484500  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102485949  CCL20; C-C motif chemokine ligand 20 [KO:K14625]
102486007  VEGFD; vascular endothelial growth factor D [KO:K05449]
102486242  RPS6KA5; ribosomal protein S6 kinase A5 [KO:K04445] [EC:2.7.11.1]
102486692  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
102486992  FRMD8; FERM domain containing 8 [KO:K23972]
102487006  CREB5; cAMP responsive element binding protein 5 [KO:K09047]
102487119  [KO:K02187] [EC:3.4.22.56]
102487413  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
102487603  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
102487885  MMP9; matrix metallopeptidase 9 [KO:K01403] [EC:3.4.24.35]
102488324  CXCL10; C-X-C motif chemokine ligand 10 [KO:K12671]
102489067  MMP3; stromelysin-1 [KO:K01394] [EC:3.4.24.17]
102489799  FADD; Fas associated via death domain [KO:K02373]
102490451  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
102490973  ITCH; itchy E3 ubiquitin protein ligase [KO:K05632] [EC:2.3.2.26]
102490996  [KO:K05405]
102491060  CYLD; CYLD lysine 63 deubiquitinase [KO:K08601] [EC:3.4.19.12]
102491199  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
102491362  CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048]
102491788  TAB3; TGF-beta activated kinase 1/MAP3K7 binding protein 3 [KO:K12793]
102492771  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
102492852  VCAM1; vascular cell adhesion molecule 1 [KO:K06527]
102492960  CSF1; colony stimulating factor 1 [KO:K05453]
102493021  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
102493692  TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158]
102493795  BIRC2; baculoviral IAP repeat containing 2 [KO:K16060]
102493843  BAG4; BCL2 associated athanogene 4 [KO:K09558]
102493856  MAP2K4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
102493858  IFNB1; interferon beta 1 [KO:K05415]
102493987  TRAF1; TNF receptor associated factor 1 [KO:K03172]
102494213  BIRC3; baculoviral IAP repeat containing 3 [KO:K16060]
102494501  CFLAR; CASP8 and FADD like apoptosis regulator [KO:K04724]
102494635  NFKBIA; NFKB inhibitor alpha [KO:K04734]
102494703  CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048]
102495046  DNM1L; dynamin 1 like [KO:K17065] [EC:3.6.5.5]
102495244  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
102495416  CX3CL1; C-X3-C motif chemokine ligand 1 [KO:K05508]
102495693  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
102496137  IL6; interleukin-6 [KO:K05405]
102496316  ADAM17; ADAM metallopeptidase domain 17 [KO:K06059] [EC:3.4.24.86]
102496404  IRF1; interferon regulatory factor 1 [KO:K09444]
102496453  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102496563  CASP10; caspase 10 [KO:K04400] [EC:3.4.22.63]
102496870  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
102497095  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
102497568  LTA; lymphotoxin alpha [KO:K05468]
102497624  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
102497846  NOD2; nucleotide binding oligomerization domain containing 2 [KO:K10165]
102497973  TNF; tumor necrosis factor [KO:K03156]
102498355  CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61]
102498451  LIF; leukemia inhibitory factor [KO:K05419]
102498502  VEGFC; vascular endothelial growth factor C [KO:K05449]
102498758  CSF2; colony stimulating factor 2 [KO:K05427]
102499419  MAP2K3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
102500092  CREB1; cAMP responsive element binding protein 1 [KO:K05870]
102500527  [KO:K10165]
102500530  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
102500729  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
102500732  MAP2K7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
102500839  XIAP; X-linked inhibitor of apoptosis [KO:K04725] [EC:2.3.2.27]
102501015  CEBPD; CCAAT/enhancer binding protein delta [KO:K10048]
102501308  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
102501622  RHBDF1; rhomboid 5 homolog 1 [KO:K27588]
102501733  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
102502163  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
102502175  [KO:K05506]
102502234  RPS6KA4; ribosomal protein S6 kinase A4 [KO:K16510] [EC:2.7.11.1]
102502622  RIPK1; receptor interacting serine/threonine kinase 1 [KO:K02861] [EC:2.7.11.1]
102503180  RIPK3; receptor interacting serine/threonine kinase 3 [KO:K08847] [EC:2.7.11.1]
106733357  [KO:K05405]
106733358  [KO:K05405]
106733575  [KO:K05405]
106733746  [KO:K05405]
106734037  [KO:K05405]
106734038  [KO:K05405]
106734039  [KO:K05405]
106736453  [KO:K00922] [EC:2.7.1.153]
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
tup04010  MAPK signaling pathway
tup04064  NF-kappa B signaling pathway
tup04120  Ubiquitin mediated proteolysis
tup04151  PI3K-Akt signaling pathway
tup04210  Apoptosis
KO pathway
ko04668   

DBGET integrated database retrieval system