Entry Name TNF signaling pathway - Pteropus alecto (black flying fox)
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 Pteropus alecto (black flying fox) [GN:
pale ]
Gene 102885752 TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158 ]
102893401 TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171 ]
102884651 BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060 ]
102882572 TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403 ]
102898592 TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404 ]
102893268 TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793 ]
102898217 CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724 ]
102880692 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
102888198 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
102878515 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048 ]
102894633 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048 ]
102882888 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048 ]
102886510 CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048 ]
102879289 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048 ]
102889014 ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
102896553 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
102884583 CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
102898128 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X3 [KO:K09049 ]
102894339 CSF1; macrophage colony-stimulating factor 1 isoform X2 [KO:K05453 ]
102893042 CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427 ]
102879561 FAS; tumor necrosis factor receptor superfamily member 6 isoform X5 [KO:K04390 ]
102881890 NOD2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165 ]
102880090 TNFRSF1B; tumor necrosis factor receptor superfamily member 1B [KO:K05141 ]
102889227 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
102880320 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
102889576 PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
102879163 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
102891637 phosphatidylinositol 3-kinase regulatory subunit gamma isoform X3 [KO:K02649 ]
102879453 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
102891786 DAB2IP; disabled homolog 2-interacting protein isoform X1 [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 Related KO pathway LinkDB All DBs
