Entry Name TNF signaling pathway - Ailuropoda melanoleuca (giant panda)
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 Ortholog table Other DBs Organism Ailuropoda melanoleuca (giant panda) [GN:
aml ]
Gene 100479926 TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158 ]
100470761 BAG4; BAG family molecular chaperone regulator 4 isoform X1 [KO:K09558 ]
100483589 TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171 ]
100477152 baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060 ]
100484077 TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X3 [KO:K04403 ]
100468085 TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404 ]
100464125 TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793 ]
100474872 CFLAR; CASP8 and FADD-like apoptosis regulator isoform X4 [KO:K04724 ]
100467906 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
100477711 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
100465448 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048 ]
100472104 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
100470867 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
100483482 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048 ]
100484531 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
100474135 ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X2 [KO:K04450 ]
100476284 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
100474261 CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
100476017 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X2 [KO:K09049 ]
100466241 growth-regulated protein homolog gamma-like isoform X1 [KO:K05505 ]
100467411 CSF1; macrophage colony-stimulating factor 1 isoform X2 [KO:K05453 ]
109488324 CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427 ]
100473767 FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390 ]
100482213 VEGFD; vascular endothelial growth factor D isoform X1 [KO:K05449 ]
100469482 NOD2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165 ]
100473387 TNFRSF1B; tumor necrosis factor receptor superfamily member 1B isoform X1 [KO:K05141 ]
100463775 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
100479294 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
100479580 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
100475291 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
100483828 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
100467916 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
100463723 DAB2IP; LOW QUALITY PROTEIN: disabled homolog 2-interacting protein [KO:K19901 ]
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 LinkDB All DBs
