Entry Name TNF signaling pathway - Theropithecus gelada (gelada)
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 Theropithecus gelada (gelada) [GN:
tge ]
Gene 112605466 CSF1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453 ]
112605791 BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060 ]
112607019 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
112608146 DAB2IP; disabled homolog 2-interacting protein isoform X1 [KO:K19901 ]
112608313 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
112608993 TNFRSF1B; tumor necrosis factor receptor superfamily member 1B [KO:K05141 ]
112612001 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649 ]
112613040 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048 ]
112614372 NOD2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165 ]
112614422 TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171 ]
112614522 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
112616616 TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793 ]
112618874 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
112619294 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
112620604 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
112621312 CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
112622249 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049 ]
112622975 TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404 ]
112624752 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
112625469 VEGFC; vascular endothelial growth factor C isoform X1 [KO:K05449 ]
112625914 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
112626456 CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427 ]
112630643 BAG4; BAG family molecular chaperone regulator 4 isoform X1 [KO:K09558 ]
112631569 FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390 ]
112632664 ATF4; cyclic AMP-dependent transcription factor ATF-4 isoform X1 [KO:K04374 ]
112633811 TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403 ]
112634042 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
112635096 TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158 ]
112636017 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
112636418 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
112636593 ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
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
