Ledgerwood E C, Pober J S, Bradley J R
Department of Medicine, University of Cambridge, United Kingdom.
Lab Invest. 1999 Sep;79(9):1041-50.
Substantial progress has been made in the last decade toward defining the signaling pathways that can be activated by TNF and identifying the relevant intracellular signaling molecules. The in vivo consequences of targeted disruption of many of the genes encoding proteins involved in TNF signaling (as discussed in this review) are quite different from those observed for knockout mutations of TNF and the TNF receptors (Erickson et al, 1994; Marino et al, 1997; Rothe et al, 1993) that use these molecules. This suggests that there is still much to be learned about the mechanisms for determining specificity in signaling. The ability to specifically manipulate the involvement of these molecules in TNF signaling, without affecting other pathways, may provide new therapeutic approaches to the many diseases in which TNF has a crucial role.
在过去十年中，在确定可被肿瘤坏死因子（TNF）激活的信号通路以及识别相关细胞内信号分子方面已经取得了重大进展。许多编码参与TNF信号传导的蛋白质的基因被靶向破坏后的体内后果（如本综述中所讨论的）与TNF和TNF受体的基因敲除突变（Erickson等人，1994年；Marino等人，1997年；Rothe等人，1993年）所观察到的后果有很大不同，而这些受体使用这些分子。这表明在确定信号传导特异性机制方面仍有许多有待了解之处。能够在不影响其他途径的情况下特异性地操纵这些分子参与TNF信号传导，可能为TNF起关键作用的许多疾病提供新的治疗方法。
