Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Cell Signal. 2021 Mar;79:109844. doi: 10.1016/j.cellsig.2020.109844. Epub 2020 Nov 24.
Signaling 'bias' is a phenomenon whereby the natural allosteric probe dependence of seven transmembrane receptors allows different receptor conformations (stabilized by different agonists) to activate some signaling pathways (coupled to pleiotropically coupled receptors) more than others at the expense of those other pathways. There are a number of relevant scenarios where such an activity could be therapeutically beneficial therefore there are practical reasons why this property of receptors should be exploited. This paper discusses recent ideas around attempts to harness this potentially useful idea and also the limitations around the current methods available to do so. Specifically, the determination of a quantitative value for the receptor bias of a given agonist that may translate to useful in vivo has been particularly elusive and studies need to be directed to solving this problem.
信号“偏向”是一种现象，即七跨膜受体的天然变构探针依赖性允许不同的受体构象（由不同的激动剂稳定）以牺牲其他途径为代价，更有效地激活一些信号通路（与多效耦合受体偶联）。有许多相关的情况，这种活性可能具有治疗益处，因此有实际的原因为什么应该利用受体的这种特性。本文讨论了围绕利用这一潜在有用的想法的最新思路，以及目前可用的方法存在的局限性。具体来说，确定给定激动剂的受体偏向的定量值可能转化为有用的体内值一直特别难以捉摸，因此需要进行研究来解决这个问题。
