Entry
Name
TNF signaling pathway - Cercocebus atys (sooty mangabey)
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 transduction
BRITE hierarchy
Pathway map
Other DBs
Organism
Cercocebus atys (sooty mangabey) [GN:
caty ]
Gene
105571321 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
105571369 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
105572871 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
105572923 TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403 ]
105574100 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049 ]
105574577 TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793 ]
105579833 ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
105580032 CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724 ]
105580103 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
105580845 TNFRSF1B; tumor necrosis factor receptor superfamily member 1B [KO:K05141 ]
105580892 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
105583011 TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158 ]
105586383 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
105587157 FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390 ]
105587262 TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171 ]
105588814 TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404 ]
105588835 NOD2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165 ]
105589639 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
105590796 BAG4; BAG family molecular chaperone regulator 4 isoform X1 [KO:K09558 ]
105591400 BIRC3; baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060 ]
105591401 BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060 ]
105591802 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048 ]
105592792 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048 ]
105593478 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
105594352 CSF1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453 ]
105594576 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
105595971 CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
105597716 PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
105598130 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
105599262 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
105599730 CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427 ]
105600049 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
Reference
Authors
Lee MY, Nam KH, Choi KC
Title
iRhoms; Its Functions and Essential Roles.
Journal
Related pathway
KO pathway