Entry Name TNF signaling pathway - Physeter macrocephalus (sperm 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 Other DBs Organism Physeter macrocephalus (sperm whale) [GN:
pcad ]
Gene 102973226 CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427 ]
102974293 CSF1; macrophage colony-stimulating factor 1 isoform X5 [KO:K05453 ]
102974369 ATF2; LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-2 [KO:K04450 ]
102975387 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048 ]
102975555 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
102976899 RIPK3; LOW QUALITY PROTEIN: receptor-interacting serine/threonine-protein kinase 3 [KO:K08847 ] [EC:2.7.11.1 ]
102977108 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
102978131 ATF6B; LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049 ]
102978952 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
102980613 TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158 ]
102981135 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
102981647 CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724 ]
102981991 BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060 ]
102983071 TNFRSF1B; tumor necrosis factor receptor superfamily member 1B isoform X1 [KO:K05141 ]
102983590 TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X3 [KO:K04403 ]
102984157 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
102985097 FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390 ]
102985635 CREB5; cyclic AMP-responsive element-binding protein 5 isoform X3 [KO:K09047 ]
102986061 TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171 ]
102986078 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X3 [KO:K09048 ]
102986098 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
102987194 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
102989082 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
102989984 VEGFC; vascular endothelial growth factor C isoform X2 [KO:K05449 ]
102991192 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649 ]
102991779 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
102992305 NOD2; LOW QUALITY PROTEIN: nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165 ]
102992944 BAG4; BAG family molecular chaperone regulator 4 isoform X1 [KO:K09558 ]
102994621 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X2 [KO:K09048 ]
102995606 TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793 ]
102996495 TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404 ]
129391322 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
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
