KEGG   PATHWAY: caty04668
Entry
caty04668                   Pathway                                
Name
TNF signaling pathway - Cercocebus atys (sooty mangabey)
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
caty04668  TNF signaling pathway
caty04668

Other DBs
GO: 0033209
Organism
Cercocebus atys (sooty mangabey) [GN:caty]
Gene
105571321  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105571369  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
105572544  EDN1; endothelin-1 [KO:K16366]
105572871  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
105572923  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
105573464  LTA; lymphotoxin-alpha [KO:K05468]
105573465  TNF; tumor necrosis factor [KO:K03156]
105573773  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
105574056  MLKL; mixed lineage kinase domain-like protein isoform X1 [KO:K08849] [EC:2.7.11.1]
105574100  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
105574577  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
105574686  RHBDF1; inactive rhomboid protein 1 isoform X1 [KO:K27588]
105574688  FIGF; vascular endothelial growth factor D [KO:K05449]
105574942  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105575713  LIF; leukemia inhibitory factor [KO:K05419]
105576775  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
105576857  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
105576876  CXCL2; C-X-C motif chemokine 2 [KO:K05505]
105576878  [KO:K05506]
105576880  [KO:K05505]
105577052  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
105577297  FADD; FAS-associated death domain protein [KO:K02373]
105577432  RELA; transcription factor p65 isoform X1 [KO:K04735]
105577443  FRMD8; FERM domain-containing protein 8 isoform X1 [KO:K23972]
105577485  RPS6KA4; ribosomal protein S6 kinase alpha-4 [KO:K16510] [EC:2.7.11.1]
105577646  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
105577687  RHBDF2; inactive rhomboid protein 2 isoform X1 [KO:K27588]
105577799  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
105577913  CASP7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
105579833  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
105579902  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
105580032  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
105580035  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
105580103  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
105580202  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
105580591  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
105580845  TNFRSF1B; tumor necrosis factor receptor superfamily member 1B [KO:K05141]
105580892  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105581389  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
105581830  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
105582081  JAG1; protein jagged-1 isoform X1 [KO:K06052]
105582292  ITCH; E3 ubiquitin-protein ligase Itchy homolog isoform X1 [KO:K05632] [EC:2.3.2.26]
105583011  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
105583640  IL18R1; interleukin-18 receptor 1 isoform X1 [KO:K05173]
105584002  IFNB1; interferon beta [KO:K05415]
105585396  CEBPB; CCAAT/enhancer-binding protein beta [KO:K10048]
105585587  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
105586304  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
105586383  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105586882  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
105586884  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
105586959  CCL20; C-C motif chemokine 20 isoform X1 [KO:K14625]
105587157  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
105587262  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
105587543  ADAM17; disintegrin and metalloproteinase domain-containing protein 17 [KO:K06059] [EC:3.4.24.86]
105588151  CX3CL1; fractalkine [KO:K05508]
105588504  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
105588770  MMP3; stromelysin-1 [KO:K01394] [EC:3.4.24.17]
105588814  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
105588835  NOD2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165]
105588862  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
105589048  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
105589068  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
105589128  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
105589331  CCL5; C-C motif chemokine 5 [KO:K12499]
105589372  CCL2; C-C motif chemokine 2 [KO:K14624]
105589639  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
105590139  VCAM1; vascular cell adhesion protein 1 [KO:K06527]
105590417  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
105590796  BAG4; BAG family molecular chaperone regulator 4 isoform X1 [KO:K09558]
105590868  FOS; proto-oncogene c-Fos [KO:K04379]
105591123  IL1B; interleukin-1 beta [KO:K04519]
105591186  BIRC8; LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 8 [KO:K04725] [EC:2.3.2.27]
105591360  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
105591400  BIRC3; baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060]
105591401  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
105591436  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
105591802  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
105592690  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
105592727  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
105592792  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
105593478  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
105593734  [KO:K02187] [EC:3.4.22.56]
105593750  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
105594352  CSF1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453]
105594576  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
105595120  BCL3; B-cell lymphoma 3 protein isoform X1 [KO:K09258]
105595383  IL6; interleukin-6 isoform X1 [KO:K05405]
105595759  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
105595971  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
105595973  JUN; transcription factor AP-1 [KO:K04448]
105596232  CXCL6; C-X-C motif chemokine 6 [KO:K05506]
105596235  CXCL1; growth-regulated alpha protein [KO:K05505]
105596237  [KO:K05505]
105596240  [KO:K05506]
105596241  [KO:K05505]
105596428  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
105596570  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
105596732  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
105596769  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105596958  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
105597716  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105597738  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
105597772  VEGFC; vascular endothelial growth factor C [KO:K05449]
105597977  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105598130  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
105598233  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105598793  MMP14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
105598850  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
105599262  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
105599730  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
105599738  IRF1; interferon regulatory factor 1 isoform X1 [KO:K09444]
105600049  DAB2IP; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
105600160  SELE; E-selectin [KO:K06494]
105600226  RIPK3; receptor-interacting serine/threonine-protein kinase 3 [KO:K08847] [EC:2.7.11.1]
105600240  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
105600386  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
105600400  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
105600720  PGAM5; serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X1 [KO:K15637] [EC:3.1.3.16]
105601165  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105601438  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
105601532  JUNB; transcription factor jun-B [KO:K09028]
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
caty04010  MAPK signaling pathway
caty04064  NF-kappa B signaling pathway
caty04120  Ubiquitin mediated proteolysis
caty04151  PI3K-Akt signaling pathway
caty04210  Apoptosis
KO pathway
ko04668   

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