KEGG   PATHWAY: mmf04668
Entry
mmf04668                    Pathway                                
Name
TNF signaling pathway - Molossus molossus (Pallas's mastiff bat)
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
mmf04668  TNF signaling pathway
mmf04668

Other DBs
GO: 0033209
Organism
Molossus molossus (Pallas's mastiff bat) [GN:mmf]
Gene
118621647  TNF; tumor necrosis factor [KO:K03156]
118623904  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
118622658  BAG4; BAG family molecular chaperone regulator 4 [KO:K09558]
118630463  ADAM17; disintegrin and metalloproteinase domain-containing protein 17 isoform X1 [KO:K06059] [EC:3.4.24.86]
118641706  RHBDF1; inactive rhomboid protein 1 isoform X1 [KO:K27588]
118633899  RHBDF2; inactive rhomboid protein 2 [KO:K27588]
118627614  FRMD8; FERM domain-containing protein 8 isoform X1 [KO:K23972]
118639212  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
118629846  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
118637497  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
118626388  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
118616944  LOW QUALITY PROTEIN: receptor-interacting serine/threonine-protein kinase 1-like [KO:K02861] [EC:2.7.11.1]
118627996  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
118628047  baculoviral IAP repeat-containing protein 3-like [KO:K16060]
118621083  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
118623445  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
118620813  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
118635648  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
118633861  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
118615560  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
118642157  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
118615122  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
118632456  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
118627223  JUN; transcription factor AP-1 [KO:K04448]
118618599  FOS; proto-oncogene c-Fos [KO:K04379]
118619138  ITCH; E3 ubiquitin-protein ligase Itchy homolog isoform X1 [KO:K05632] [EC:2.3.2.26]
118625230  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
118641294  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
118634140  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
118641186  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
118641187  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
118621004  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
118621005  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
118618639  CEBPB; CCAAT/enhancer-binding protein beta [KO:K10048]
118620900  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
118634183  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
118635619  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
118622317  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
118632312  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
118617230  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
118628367  RELA; transcription factor p65 [KO:K04735]
118624789  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
118639002  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
118628434  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
118640210  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
118642307  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
118639959  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X5 [KO:K04445] [EC:2.7.11.1]
118628283  RPS6KA4; ribosomal protein S6 kinase alpha-4 [KO:K16510] [EC:2.7.11.1]
118624959  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
118620417  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
118628166  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
118629628  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
118637511  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
118615816  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
118625175  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
118623538  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
118620061  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
118621725  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
118639126  RIPK3; receptor-interacting serine/threonine-protein kinase 3 isoform X1 [KO:K08847] [EC:2.7.11.1]
118628258  FADD; FAS-associated death domain protein [KO:K02373]
118625346  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
118625231  CASP10; caspase-10 isoform X1 [KO:K04400] [EC:3.4.22.63]
118632454  CASP7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
118622705  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
118639478  MLKL; mixed lineage kinase domain-like protein isoform X1 [KO:K08849] [EC:2.7.11.1]
118639817  PGAM5; serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X1 [KO:K15637] [EC:3.1.3.16]
118624463  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
118638506  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD [KO:K08601] [EC:3.4.19.12]
118635819  E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
118634634  C-C motif chemokine 2-like [KO:K14624]
118634388  CCL5; C-C motif chemokine 5 [KO:K12499]
118625758  CCL20; C-C motif chemokine 20 [KO:K14625]
118626364  growth-regulated protein homolog gamma-like [KO:K05505]
118643206  growth-regulated protein homolog [KO:K05505]
118643274  growth-regulated protein homolog gamma-like [KO:K05505]
118626277  CXCL5; C-X-C motif chemokine 5 [KO:K05506]
118618117  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
118639024  CX3CL1; fractalkine [KO:K05508]
118637506  CSF1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453]
118615980  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
118632575  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
118631027  IL18R1; interleukin-18 receptor 1 isoform X1 [KO:K05173]
118618635  JAG1; protein jagged-1 [KO:K06052]
118630740  IL1B; interleukin-1 beta [KO:K04519]
118620458  IL6; interleukin-6 isoform X1 [KO:K05405]
118616314  IL15; interleukin-15 isoform X1 [KO:K05433]
118639768  LIF; leukemia inhibitory factor isoform X1 [KO:K05419]
118621917  LTA; lymphotoxin-alpha [KO:K05468]
118639536  BCL3; B-cell lymphoma 3 protein [KO:K09258]
118634253  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
118621121  TNFAIP3; tumor necrosis factor alpha-induced protein 3 isoform X1 [KO:K11859] [EC:3.4.19.12]
118630181  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
118616288  JUNB; transcription factor jun-B [KO:K09028]
118628226  stromelysin-1-like [KO:K01394] [EC:3.4.24.17]
118618723  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
118616019  MMP14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
118626932  EDN1; endothelin-1 [KO:K16366]
118636328  VEGFD; vascular endothelial growth factor D [KO:K05449]
118622788  VEGFC; vascular endothelial growth factor C [KO:K05449]
118639113  NOD2; nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165]
118615517  ICAM1; intercellular adhesion molecule 1 isoform X1 [KO:K06490]
118637866  E-selectin-like [KO:K06494]
118637380  VCAM1; vascular cell adhesion protein 1 isoform X1 [KO:K06527]
118637857  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
118626273  TNFRSF1B; tumor necrosis factor receptor superfamily member 1B [KO:K05141]
118633499  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
118632927  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118626944  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118617106  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118626685  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
118642883  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
118616460  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
118640620  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
118619617  LOW QUALITY PROTEIN: RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
118630299  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
118638405  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
118629895  disabled homolog 2-interacting protein isoform X1 [KO:K19901]
118643572  IRF1; interferon regulatory factor 1 isoform X1 [KO:K09444]
118629329  IFNB1; interferon beta [KO:K05415]
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
mmf04010  MAPK signaling pathway
mmf04064  NF-kappa B signaling pathway
mmf04120  Ubiquitin mediated proteolysis
mmf04151  PI3K-Akt signaling pathway
mmf04210  Apoptosis
KO pathway
ko04668   
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