Entry Name TNF signaling pathway - Bos taurus (cow)
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 Bos taurus (cow) [GN:
bta ]
Gene 280840 LIF; leukemia inhibitory factor precursor [KO:K05419 ]
281094 CSF1; macrophage colony-stimulating factor 1 precursor [KO:K05453 ]
281095 CSF2; granulocyte-macrophage colony-stimulating factor precursor [KO:K05427 ]
281212 GRO1; growth-regulated protein homolog alpha precursor [KO:K05505 ]
281214 CXCL2; growth-regulated protein homolog gamma precursor [KO:K05505 ]
281713 CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870 ]
281715 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
281839 ICAM1; intercellular adhesion molecule 1 precursor [KO:K06490 ]
282081 SOCS3; suppressor of cytokine signaling 3 [KO:K04696 ]
282118 VCAM1; vascular cell adhesion molecule 1 precursor [KO:K06527 ]
282122 VEGFC; vascular endothelial growth factor C precursor [KO:K05449 ]
282306 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
282307 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649 ]
282308 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
282488 FAS; tumor necrosis factor receptor superfamily member 6 precursor [KO:K04390 ]
282527 TNFRSF1A; tumor necrosis factor receptor superfamily member 1A precursor [KO:K03158 ]
286799 VEGFD; vascular endothelial growth factor D precursor [KO:K05449 ]
286865 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
338033 TNFRSF1B; tumor necrosis factor receptor superfamily member 1B precursor [KO:K05141 ]
338319 CEBPB; CCAAT/enhancer-binding protein beta [KO:K10048 ]
407221 IL18R1; interleukin-18 receptor 1 isoform X2 [KO:K05173 ]
444867 NOD2; nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165 ]
493720 FADD; FAS-associated death domain protein [KO:K02373 ]
497199 CFLAR; CASP8 and FADD-like apoptosis regulator [KO:K04724 ]
504531 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
504707 TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171 ]
509107 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
509827 ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450 ]
513010 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048 ]
513105 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
513928 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049 ]
514386 BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060 ]
516353 BAG4; BAG family molecular chaperone regulator 4 [KO:K09558 ]
517541 ADAM17; disintegrin and metalloproteinase domain-containing protein 17 isoform X1 [KO:K06059 ] [EC:3.4.24.86 ]
517948 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
519958 TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403 ]
521987 IFI47; interferon gamma inducible protein 47 [KO:K17072 ]
529566 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X5 [KO:K09048 ]
534129 CREB5; cyclic AMP-responsive element-binding protein 5 [KO:K09047 ]
539314 BIRC2; baculoviral IAP repeat-containing protein 2 isoform X2 [KO:K16060 ]
540203 TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404 ]
541268 DAB2IP; disabled homolog 2-interacting protein [KO:K19901 ]
613667 CXCL3; chemokine (C-X-C motif) ligand 3 precursor [KO:K05505 ]
615107 CXCL10; C-X-C motif chemokine 10 precursor [KO:K12671 ]
616115 NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580 ]
785086 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
787278 MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431 ] [EC:2.7.12.2 ]
788288 TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793 ]
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
