Entry
Name
TNF signaling pathway - Propithecus coquereli (Coquerel's sifaka)
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
Propithecus coquereli (Coquerel's sifaka) [GN:
pcoq ]
Gene
105805081 TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158 ]
105805175 TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403 ]
105805232 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
105805755 TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793 ]
105806240 PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
105808868 NOD2; nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165 ]
105809025 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
105811104 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
105811984 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048 ]
105814042 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
105815570 ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
105817861 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049 ]
105818191 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
105819191 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
105819344 TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404 ]
105820021 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
105821018 CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427 ]
105821904 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048 ]
105822691 FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390 ]
105823400 TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171 ]
105823945 CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870 ]
105824987 TNFRSF1B; tumor necrosis factor receptor superfamily member 1B isoform X1 [KO:K05141 ]
105824997 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
105825541 CSF1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453 ]
105826540 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
105826612 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
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