Entry Name TNF signaling pathway - Equus caballus (horse)
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 transductionBRITE hierarchy
Pathway map Other DBs Organism Equus caballus (horse) [GN:
ecb ]
Gene 100033981 CSF2; granulocyte-macrophage colony-stimulating factor precursor [KO:K05427 ]
100034121 CXCL1; chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha) precursor [KO:K05505 ]
100050227 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649 ]
100050877 VEGFD; vascular endothelial growth factor D isoform X1 [KO:K05449 ]
100051087 TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793 ]
100051623 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
100051753 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
100053304 ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
100054803 CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
100055840 TNFRSF1B; tumor necrosis factor receptor superfamily member 1B isoform X3 [KO:K05141 ]
100056258 MIP-2BETA; uncharacterized protein LOC100056258 precursor [KO:K05505 ]
100057002 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048 ]
100057730 BAG4; BAG family molecular chaperone regulator 4 isoform X1 [KO:K09558 ]
100058141 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
100059123 NOD2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165 ]
100059348 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049 ]
100059548 TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158 ]
100060433 TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404 ]
100060890 VEGFC; vascular endothelial growth factor C isoform X1 [KO:K05449 ]
100062307 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
100063153 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048 ]
100064828 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
100065824 TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171 ]
100066388 CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870 ]
100067794 CREB3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
100067894 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X4 [KO:K02580 ]
100068181 CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724 ]
100070300 TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403 ]
100070334 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
100071474 CEBPB; CCAAT/enhancer-binding protein beta isoform X1 [KO:K10048 ]
100071639 FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390 ]
100071680 DAB2IP; disabled homolog 2-interacting protein isoform X8 [KO:K19901 ]
100146348 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
100146493 CSF1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453 ]
Reference Authors Chu WM
Title Tumor necrosis factor.
Journal 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 Reference Authors Newton K, Dixit VM
Title Signaling in innate immunity and inflammation.
Journal 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 Reference Authors Naude PJ, den Boer JA, Luiten PG, Eisel UL
Title Tumor necrosis factor receptor cross-talk.
Journal Reference Authors Faustman D, Davis M
Title TNF receptor 2 pathway: drug target for autoimmune diseases.
Journal 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 Reference Authors Lee MY, Nam KH, Choi KC
Title iRhoms; Its Functions and Essential Roles.
Journal Related KO pathway
