Tumour necrosis factors receptor associated signalling molecules and theirrole in activation of apoptosis, JNK and NF-kappa B

Tumour necrosis factor (TNF) is a pleiotropic cytokine that mediates apopto sis, cell proliferation, immunomodulation, inflammation, viral replication, allergy, arthritis, septic shock, insulin resistance, autoimmune diseases, and other pathological conditions. TNF transduces these cellular responses through two distinct receptors: type I, which are expressed on all cell ty pes, and type II, which are expressed only on cells of the immune system an d endothelial cells. At the cellular level, these receptors activate the pa thways leading to the activation of transcription factors NF-kappaB and AP- 1, apoptosis and proliferation, and mitogen activated protein kinases. None of these receptors exhibit am enzymatic activity but the signals are trans mitted through the recruitment of more than a dozen different signalling pr oteins, which together form signalling cascades. Inhibitors of TNF signalli ng have therapeutic value as indicated by the approval of the soluble TNF r eceptors and anti-TNF antibodies for rheumatoid arthritis and for inflammat ory bowl disease.