Faculty of Medicine, Department of Physiology, Semmelweis University, Budapest, Hungary.
Acta Physiol (Oxf). 2012 Apr;204(4):469-78. doi: 10.1111/j.1748-1716.2012.02414.x. Epub 2012 Feb 18.
Studies on the regulation of cellular activity mainly focus on signal generation, but termination of signalling is an equally important factor, which prevents inappropriate activity. This paper reviews the mechanisms, which can cause termination of signalling, and provides examples that illustrate the importance of these processes. Inactivation of voltage-gated Na(+) channels and the photoactivated rhodopsin molecule is caused by rapid conformational rearrangements. Negative feedback can also contribute to the termination of signalling for various mechanisms, including plasma membrane ion channels or cAMP signal generation. In immune cells, the tyrosine-based inhibitory motif (ITIM)-containing molecules are essential negative regulatory components. Desensitization of G-protein-coupled receptors can occur with homologous and heterologous mechanisms, mediated by β-arrestin molecules and second messenger-induced kinases respectively. In NF-κB signalling, resynthetized IκB and other enzymes form negative feedback loops. GTPase-activating proteins are also dedicated to termination of signalling, because they can switch off the small G proteins by increasing their endogenous GTP hydrolysis. In many systems, signal termination is a result of a combined action of several different mechanisms, which underlines the importance of these processes.
细胞活动的调节主要集中在信号的产生上，但信号的终止同样是一个重要的因素，可以防止不适当的活动。本文综述了可导致信号终止的机制，并提供了说明这些过程重要性的实例。快速构象重排可导致电压门控 Na(+)通道和光激活视紫红质分子失活。负反馈也可以为各种机制（包括质膜离子通道或 cAMP 信号产生）的信号终止做出贡献。在免疫细胞中，含酪氨酸的抑制基序（ITIM）的分子是必不可少的负调节成分。G 蛋白偶联受体的脱敏可以通过同源和异源机制发生，分别由β-arrestin 分子和第二信使诱导的激酶介导。在 NF-κB 信号转导中，重新合成的 IκB 和其他酶形成负反馈环。GTPase 激活蛋白也专门用于终止信号，因为它们可以通过增加内源性 GTP 水解来关闭小 G 蛋白。在许多系统中，信号终止是几种不同机制共同作用的结果，这突显了这些过程的重要性。
