KEGG   PATHWAY: mcal04668
Entry
mcal04668                   Pathway                                
Name
TNF signaling pathway - Mus caroli (Ryukyu mouse)
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
mcal04668  TNF signaling pathway
mcal04668

Other DBs
GO: 0033209
Organism
Mus caroli (Ryukyu mouse) [GN:mcal]
Gene
110284110  Tnf; tumor necrosis factor [KO:K03156]
110284314  Lta; lymphotoxin-alpha [KO:K05468]
110284809  Map3k8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
110285285  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
110285316  Rps6ka4; ribosomal protein S6 kinase alpha-4 isoform X1 [KO:K16510] [EC:2.7.11.1]
110285584  Frmd8; FERM domain-containing protein 8 isoform X1 [KO:K23972]
110285614  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X2 [KO:K05870]
110285655  Fas; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
110285703  Rela; transcription factor p65 [KO:K04735]
110285885  Casp7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
110286367  Atf2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
110286671  Xiap; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
110286971  Tab3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X2 [KO:K12793]
110287188  Ikbkg; NF-kappa-B essential modulator isoform X4 [KO:K07210]
110287326  Vegfd; vascular endothelial growth factor D [KO:K05449]
110288090  [KO:K11987] [EC:1.14.99.1]
110288092  [KO:K11987] [EC:1.14.99.1]
110288093  [KO:K11987] [EC:1.14.99.1]
110289299  Cebpb; CCAAT/enhancer-binding protein beta [KO:K10048]
110289497  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X2 [KO:K09048]
110289943  Traf1; TNF receptor-associated factor 1 [KO:K03172]
110289986  Traf2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
110290048  Mmp9; matrix metalloproteinase-9 isoform X1 [KO:K01403] [EC:3.4.24.35]
110290100  Il1b; interleukin-1 beta [KO:K04519]
110290798  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
110290917  Vcam1; vascular cell adhesion protein 1 [KO:K06527]
110291231  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
110291408  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
110291496  Csf1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453]
110291975  Casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
110292183  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110292293  Map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
110292340  [KO:K11987] [EC:1.14.99.1]
110292423  Jun; transcription factor AP-1 [KO:K04448]
110292554  Tnfrsf1b; tumor necrosis factor receptor superfamily member 1B [KO:K05141]
110292624  [KO:K02649]
110292754  Creb3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
110293482  Cflar; CASP8 and FADD-like apoptosis regulator isoform X2 [KO:K04724]
110293791  Ifnb1; interferon beta [KO:K05415]
110293896  Cxcl10; C-X-C motif chemokine 10 [KO:K12671]
110294148  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
110294306  Pgam5; serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X1 [KO:K15637] [EC:3.1.3.16]
110294442  [KO:K05505]
110294443  [KO:K05505]
110294471  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110295209  [KO:K05505]
110295330  Il6; interleukin-6 [KO:K05405]
110295457  [KO:K05506]
110296066  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
110296203  Creb5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
110296205  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
110296886  Traf5; TNF receptor-associated factor 5 [KO:K09849]
110297609  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110297836  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
110298222  Fadd; FAS-associated death domain protein [KO:K02373]
110299300  Bcl3; B-cell lymphoma 3 protein [KO:K09258]
110299603  Map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
110299742  Cyld; ubiquitin carboxyl-terminal hydrolase CYLD isoform X2 [KO:K08601] [EC:3.4.19.12]
110299851  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
110299855  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
110299917  Bag4; BAG family molecular chaperone regulator 4 [KO:K09558]
110299961  Junb; transcription factor jun-B [KO:K09028]
110300158  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
110300171  Vegfc; vascular endothelial growth factor C [KO:K05449]
110300342  Il15; interleukin-15 isoform X1 [KO:K05433]
110300504  Cx3cl1; fractalkine [KO:K05508]
110300541  Tradd; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
110300637  Nod2; nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165]
110300641  Mlkl; mixed lineage kinase domain-like protein [KO:K08849] [EC:2.7.11.1]
110301325  Icam1; intercellular adhesion molecule 1 [KO:K06490]
110301355  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
110301502  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
110301861  Birc2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
110301975  [KO:K01394] [EC:3.4.24.17]
110302224  Sele; E-selectin [KO:K06494]
110302303  [KO:K16060]
110303143  Tnfaip3; tumor necrosis factor alpha-induced protein 3 isoform X1 [KO:K11859] [EC:3.4.19.12]
110303337  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
110303338  Map3k5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
110303346  Ccl20; C-C motif chemokine 20 isoform X1 [KO:K14625]
110303471  Il18r1; interleukin-18 receptor 1 [KO:K05173]
110303600  Tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
110304169  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
110304647  Rhbdf1; inactive rhomboid protein 1 isoform X1 [KO:K27588]
110304684  Map2k6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
110304803  Map2k4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
110304892  Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
110304930  Socs3; suppressor of cytokine signaling 3 [KO:K04696]
110304977  Map2k3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
110305192  [KO:K14624]
110305385  [KO:K17072]
110305493  Rhbdf2; inactive rhomboid protein 2 isoform X1 [KO:K27588]
110305657  Irf1; interferon regulatory factor 1 [KO:K09444]
110305824  Ccl5; C-C motif chemokine 5 [KO:K12499]
110305912  Lif; leukemia inhibitory factor isoform X1 [KO:K05419]
110305913  [KO:K14624]
110305989  Csf2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
110306467  Adam17; disintegrin and metalloproteinase domain-containing protein 17 [KO:K06059] [EC:3.4.24.86]
110306698  Rps6ka5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
110306864  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
110306954  Traf3; TNF receptor-associated factor 3 [KO:K03174]
110307022  Akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110307063  Fos; proto-oncogene c-Fos [KO:K04379]
110307946  Ripk1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
110308009  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
110308576  Edn1; endothelin-1 [KO:K16366]
110308920  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
110309210  Mmp14; matrix metalloproteinase-14 isoform X1 [KO:K07763] [EC:3.4.24.80]
110309235  Dab2ip; disabled homolog 2-interacting protein isoform X11 [KO:K19901]
110309461  Ripk3; receptor-interacting serine/threonine-protein kinase 3 [KO:K08847] [EC:2.7.11.1]
110309477  Itch; E3 ubiquitin-protein ligase Itchy homolog [KO:K05632] [EC:2.3.2.26]
110310212  Tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
110310272  Jag1; protein jagged-1 [KO:K06052]
110310868  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
110310902  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
110310903  Mapk11; mitogen-activated protein kinase 11 isoform X2 [KO:K04441] [EC:2.7.11.24]
110311382  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
110311391  Dnm1l; dynamin-1-like protein isoform X6 [KO:K17065] [EC:3.6.5.5]
110312437  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
110312537  Atf6b; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
110312562  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
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
mcal04010  MAPK signaling pathway
mcal04064  NF-kappa B signaling pathway
mcal04120  Ubiquitin mediated proteolysis
mcal04151  PI3K-Akt signaling pathway
mcal04210  Apoptosis
KO pathway
ko04668   

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