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Pathway Description
TNF/Stress Related Signaling
Homo sapiens
Protein Pathway
Tumour necrosis factor alpha (TNF-a) is a cytokine that activates TNF rector 1 (TNFR1) signalling complex. TNFR1 mediates cell death signalling and inflammation in response to cytokines, bacteria and cellular stress. The classical NFkB pathway involves activation of TNF receptor associated factor 2, receptor interacting serine/threonine protein kinase and death domains which activate the IKK complex, phosphorylating the IKB proteins triggering their degradation resulting in NF-kB dimers dissociation and release. Caspase 2 interacts with TNF-receptor associated factor 2 and receptor interacting serine/threonine protein kinase to activate NFkB. Mitogen activated protein kinases of the MAP3K family are also involved in TNFR1-mediated IKK activation. Mitogen activated kinases can phosphorylate IKK to activate it as well. Activation of Mitogen-activated protein kinase 8 and 14 are involved in the cross-talk of other inflammatory pathways.
References
TNF/Stress Related Signaling References
https://cgap.nci.nih.gov/Pathways/BioCarta/h_stressPathway
Proudfoot A, Bayliffe A, O'Kane CM, Wright T, Serone A, Bareille PJ, Brown V, Hamid UI, Chen Y, Wilson R, Cordy J, Morley P, de Wildt R, Elborn S, Hind M, Chilvers ER, Griffiths M, Summers C, McAuley DF: Novel anti-tumour necrosis factor receptor-1 (TNFR1) domain antibody prevents pulmonary inflammation in experimental acute lung injury. Thorax. 2018 Aug;73(8):723-730. doi: 10.1136/thoraxjnl-2017-210305. Epub 2018 Jan 29.
Pubmed: 29382797
Wajant H, Scheurich P: TNFR1-induced activation of the classical NF-kappaB pathway. FEBS J. 2011 Apr;278(6):862-76. doi: 10.1111/j.1742-4658.2011.08015.x. Epub 2011 Feb 8.
Pubmed: 21232017
Waetzig GH, Seegert D, Rosenstiel P, Nikolaus S, Schreiber S: p38 mitogen-activated protein kinase is activated and linked to TNF-alpha signaling in inflammatory bowel disease. J Immunol. 2002 May 15;168(10):5342-51.
Pubmed: 11994493
Lamkanfi M, D'hondt K, Vande Walle L, van Gurp M, Denecker G, Demeulemeester J, Kalai M, Declercq W, Saelens X, Vandenabeele P: A novel caspase-2 complex containing TRAF2 and RIP1. J Biol Chem. 2005 Feb 25;280(8):6923-32. doi: 10.1074/jbc.M411180200. Epub 2004 Dec 8.
Pubmed: 15590671
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