KEGG   PATHWAY: pcoq04668
Entry
pcoq04668                   Pathway                                
Name
TNF signaling pathway - Propithecus coquereli (Coquerel's sifaka)
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
pcoq04668  TNF signaling pathway
pcoq04668

Other DBs
GO: 0033209
Organism
Propithecus coquereli (Coquerel's sifaka) [GN:pcoq]
Gene
105804916  ITCH; E3 ubiquitin-protein ligase Itchy homolog isoform X1 [KO:K05632] [EC:2.3.2.26]
105805081  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
105805175  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
105805232  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
105805315  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
105805435  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
105805749  FIGF; vascular endothelial growth factor D [KO:K05449]
105805755  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
105806240  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105806347  JUN; transcription factor AP-1 [KO:K04448]
105806730  ADAM17; disintegrin and metalloproteinase domain-containing protein 17 [KO:K06059] [EC:3.4.24.86]
105807166  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
105807372  [KO:K09047]
105807585  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
105807825  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
105807904  JUNB; transcription factor jun-B [KO:K09028]
105807933  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
105807976  MLKL; mixed lineage kinase domain-like protein [KO:K08849] [EC:2.7.11.1]
105808308  IL18R1; interleukin-18 receptor 1 isoform X1 [KO:K05173]
105808769  CCL20; C-C motif chemokine 20 isoform X1 [KO:K14625]
105808865  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
105808868  NOD2; nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165]
105809025  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
105810111  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
105810199  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105810397  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105810783  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105811104  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
105811984  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
105812191  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
105812227  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
105812606  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105812625  TRAF3; TNF receptor-associated factor 3 [KO:K03174]
105812700  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
105812766  RIPK3; receptor-interacting serine/threonine-protein kinase 3 isoform X1 [KO:K08847] [EC:2.7.11.1]
105813187  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
105813535  [KO:K14624]
105813849  CCL5; C-C motif chemokine 5 [KO:K12499]
105813949  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
105813961  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
105814042  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
105814481  MMP14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
105815343  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
105815570  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
105815749  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
105815846  BAG4; BAG family molecular chaperone regulator 4 [KO:K09558]
105815999  [KO:K04440] [EC:2.7.11.24]
105816051  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
105816099  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
105816267  VEGFC; vascular endothelial growth factor C [KO:K05449]
105817473  EDN1; endothelin-1 [KO:K16366]
105817706  BCL3; B-cell lymphoma 3 protein [KO:K09258]
105817861  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
105817905  TNF; tumor necrosis factor isoform X1 [KO:K03156]
105817906  LTA; lymphotoxin-alpha [KO:K05468]
105818077  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
105818191  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105818634  CEBPB; CCAAT/enhancer-binding protein beta [KO:K10048]
105818690  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
105818749  [KO:K04415] [EC:2.7.11.25]
105818750  [KO:K04415] [EC:2.7.11.25]
105818793  VCAM1; vascular cell adhesion protein 1 isoform X1 [KO:K06527]
105819115  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
105819191  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
105819344  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
105819401  CFLAR; CASP8 and FADD-like apoptosis regulator [KO:K04724]
105819477  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
105819687  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
105819831  FOS; proto-oncogene c-Fos [KO:K04379]
105820021  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
105820326  IL1B; interleukin-1 beta [KO:K04519]
105820591  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105820660  JAG1; protein jagged-1 [KO:K06052]
105820722  PGAM5; serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X1 [KO:K15637] [EC:3.1.3.16]
105820857  CX3CL1; fractalkine [KO:K05508]
105821018  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
105821023  IRF1; interferon regulatory factor 1 [KO:K09444]
105821108  SELE; E-selectin [KO:K06494]
105821284  LIF; leukemia inhibitory factor [KO:K05419]
105821530  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
105821904  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
105822157  [KO:K01394] [EC:3.4.24.17]
105822245  [KO:K01394] [EC:3.4.24.17]
105822276  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
105822279  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
105822445  IL6; interleukin-6 [KO:K05405]
105822593  RHBDF1; inactive rhomboid protein 1 [KO:K27588]
105822691  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
105822828  [KO:K05506]
105822925  RPS6KA5; ribosomal protein S6 kinase alpha-5 [KO:K04445] [EC:2.7.11.1]
105823104  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
105823400  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
105823643  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
105823945  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
105824014  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
105824147  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
105824261  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
105824538  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
105824710  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
105824784  RHBDF2; inactive rhomboid protein 2 isoform X1 [KO:K27588]
105824987  TNFRSF1B; tumor necrosis factor receptor superfamily member 1B isoform X1 [KO:K05141]
105824997  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
105825541  CSF1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453]
105826018  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
105826431  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
105826457  DAB2IP; disabled homolog 2-interacting protein [KO:K19901]
105826540  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
105826612  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
105826835  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
105827006  IFNB1; interferon beta [KO:K05415]
105827162  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
105827289  RPS6KA4; ribosomal protein S6 kinase alpha-4 [KO:K16510] [EC:2.7.11.1]
105827383  RELA; transcription factor p65 isoform X1 [KO:K04735]
105827455  FRMD8; FERM domain-containing protein 8 [KO:K23972]
105827473  FADD; FAS-associated death domain protein [KO:K02373]
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
pcoq04010  MAPK signaling pathway
pcoq04064  NF-kappa B signaling pathway
pcoq04120  Ubiquitin mediated proteolysis
pcoq04151  PI3K-Akt signaling pathway
pcoq04210  Apoptosis
KO pathway
ko04668   

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