MacEwan David J
Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.
Cell Signal. 2002 Jun;14(6):477-92. doi: 10.1016/s0898-6568(01)00262-5.
Tumour necrosis factor-alpha (TNF alpha) is a multifunctional cytokine belonging to a family of ligands with an associated family of receptor proteins. The pleiotropic actions of TNF range from proliferative responses such as cell growth and differentiation, to inflammatory effects and the mediation of immune responses, to destructive cellular outcomes such as apoptotic and necrotic cell death mechanisms. Activated TNF receptors mediate the association of distinct adaptor proteins that regulate a variety of signalling processes including kinase or phosphatase activation, lipase stimulation, and protease induction. Moreover, the cytokine regulates the activities of transcription factors, heterotrimeric or monomeric G-proteins and calcium ion homeostasis in order to orchestrate its cellular functions. This review addresses the structural basis of TNF signalling, the pathways employed with their cellular consequences, and focuses on the specific role played by each of the two TNF receptor isotypes, TNFR1 and TNFR2.
肿瘤坏死因子-α（TNFα）是一种多功能细胞因子，属于一个配体家族，该家族有相关的受体蛋白家族。TNF的多效性作用范围广泛，从细胞生长和分化等增殖反应，到炎症效应和免疫反应的介导，再到凋亡和坏死性细胞死亡机制等破坏性细胞结果。活化的TNF受体介导不同衔接蛋白的结合，这些衔接蛋白调节多种信号传导过程，包括激酶或磷酸酶激活、脂肪酶刺激和蛋白酶诱导。此外，该细胞因子调节转录因子、异源三聚体或单体G蛋白的活性以及钙离子稳态，以协调其细胞功能。本综述阐述了TNF信号传导的结构基础、所采用的途径及其细胞后果，并重点关注两种TNF受体亚型TNFR1和TNFR2各自所起的特定作用。
