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.

TNF/Stress Related Signaling References