TNF and MAP kinase signalling pathways

The binding of tumour necrosis factor alpha (TNFalpha) to cell surface receptors engages multiple signal transduction pathways, including three groups of mitogen-activated protein (MAP) kinases: extracellular-signal-regulated kinases (ERKs); the cJun NH2-terminal kinases (JNKs); and the p38 MAP kinases. These MAP kinase signalling pathways induce a secondary response by increasing the expression of several inflammatory cytokines (including TNFalpha) that contribute to the biological activity of TNFalpha. MAP kinases therefore function both upstream and down-stream of signalling by TNFalpha receptors. Here we review mechanisms that mediate these actions of MAP kinases during the response to TNFalpha