Entry Name TNF signaling pathway - Delphinapterus leucas (beluga whale)
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 Delphinapterus leucas (beluga whale) [GN:
dle ]
Gene 111176656 TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158 ]
111179654 TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171 ]
111168370 BIRC3; baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060 ]
111186464 TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403 ]
111166813 TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404 ]
111168401 TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793 ]
111171724 CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724 ]
111179110 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
111171769 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
111167181 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
111188007 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
111166195 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048 ]
111177962 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
111183987 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
111172890 ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
111186212 ATF4; cyclic AMP-dependent transcription factor ATF-4 isoform X1 [KO:K04374 ]
111180225 CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
111170946 ATF6B; LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049 ]
111180064 CSF1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453 ]
111182406 CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427 ]
111172519 FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390 ]
111166693 T-cell-specific guanine nucleotide triphosphate-binding protein 1-like [KO:K17072 ]
111164994 NOD2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165 ]
111187038 TNFRSF1B; tumor necrosis factor receptor superfamily member 1B [KO:K05141 ]
111173839 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
111179235 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
111187262 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
111166652 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
111185984 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
111175760 phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
111177256 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
