TNF signaling pathway - Mus musculus (house mouse)
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.
Environmental Information Processing; Signal transduction
Pathway map Ortholog table
Mus musculus (house mouse) [GN:
21937 Tnfrsf1a; tumor necrosis factor receptor superfamily, member 1a [KO: K03158]
71609 Tradd; TNFRSF1A-associated via death domain [KO: K03171]
22033 Traf5; TNF receptor-associated factor 5 [KO: K09849]
11797 Birc2; baculoviral IAP repeat-containing 2 [KO: K16060]
11796 Birc3; baculoviral IAP repeat-containing 3 [KO: K16060]
66513 Tab1; TGF-beta activated kinase 1/MAP3K7 binding protein 1 [KO: K04403]
68652 Tab2; TGF-beta activated kinase 1/MAP3K7 binding protein 2 [KO: K04404]
66724 Tab3; TGF-beta activated kinase 1/MAP3K7 binding protein 3 [KO: K12793]
12633 Cflar; CASP8 and FADD-like apoptosis regulator [KO: K04724]
12608 Cebpb; CCAAT/enhancer binding protein (C/EBP), beta [KO: K10048]
16151 Ikbkg; inhibitor of kappaB kinase gamma [KO: K07210]
18035 Nfkbia; nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha [KO: K04734]
19697 Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO: K04735]
18033 Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 [KO: K02580]
12912 Creb1; cAMP responsive element binding protein 1 [KO: K05870]
12913 Creb3; cAMP responsive element binding protein 3 [KO: K09048]
26427 Creb3l1; cAMP responsive element binding protein 3-like 1 [KO: K09048]
208647 Creb3l2; cAMP responsive element binding protein 3-like 2 [KO: K09048]
208677 Creb3l3; cAMP responsive element binding protein 3-like 3 [KO: K09048]
78284 Creb3l4; cAMP responsive element binding protein 3-like 4 [KO: K09048]
11909 Atf2; activating transcription factor 2 [KO: K04450]
11911 Atf4; activating transcription factor 4 [KO: K04374]
231991 Creb5; cAMP responsive element binding protein 5 [KO: K09047]
12915 Atf6b; activating transcription factor 6 beta [KO: K09049]
14082 Fadd; Fas (TNFRSF6)-associated via death domain [KO: K02373]
20293 Ccl12; chemokine (C-C motif) ligand 12 [KO: K14624]
20297 Ccl20; chemokine (C-C motif) ligand 20 [KO: K14625]
14825 Cxcl1; chemokine (C-X-C motif) ligand 1 [KO: K05505]
20310 Cxcl2; chemokine (C-X-C motif) ligand 2 [KO: K05505]
20311 Cxcl5; chemokine (C-X-C motif) ligand 5 [KO: K05506]
15945 Cxcl10; chemokine (C-X-C motif) ligand 10 [KO: K12671]
20312 Cx3cl1; chemokine (C-X3-C motif) ligand 1 [KO: K05508]
12977 Csf1; colony stimulating factor 1 (macrophage) [KO: K05453]
12981 Csf2; colony stimulating factor 2 (granulocyte-macrophage) [KO: K05427]
14102 Fas; Fas (TNF receptor superfamily member 6) [KO: K04390]
12702 Socs3; suppressor of cytokine signaling 3 [KO: K04696]
22029 Traf1; TNF receptor-associated factor 1 [KO: K03172]
15953 Ifi47; interferon gamma inducible protein 47 [KO: K17072]
22341 Vegfc; vascular endothelial growth factor C [KO: K05449]
14205 Vegfd; vascular endothelial growth factor D [KO: K05449]
257632 Nod2; nucleotide-binding oligomerization domain containing 2 [KO: K10165]
15894 Icam1; intercellular adhesion molecule 1 [KO: K06490]
22329 Vcam1; vascular cell adhesion molecule 1 [KO: K06527]
21938 Tnfrsf1b; tumor necrosis factor receptor superfamily, member 1b [KO: K05141]
22031 Traf3; TNF receptor-associated factor 3 [KO: K03174]
18706 Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO: K00922] [EC: 184.108.40.206]
18707 Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO: K00922] [EC: 220.127.116.11]
74769 Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO: K00922] [EC: 18.104.22.168]
18709 Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO: K02649]
18708 Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO: K02649]
18710 Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO: K02649]
69601 Dab2ip; disabled 2 interacting protein [KO: K19901]
Tumor necrosis factor.
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Ochsner J 13:119-30 (2013)
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Signaling in innate immunity and inflammation.
Pomerantz JL, Baltimore D
NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase.
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Tumor necrosis factor receptor cross-talk.
Faustman D, Davis M
TNF receptor 2 pathway: drug target for autoimmune diseases.
Chan FK, Shisler J, Bixby JG, Felices M, Zheng L, Appel M, Orenstein J, Moss B, Lenardo MJ
A role for tumor necrosis factor receptor-2 and receptor-interacting protein in programmed necrosis and antiviral responses.
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