Department of Physiology, Semmelweis University, Budapest, Hungary.
Physiol Rev. 2012 Jan;92(1):237-72. doi: 10.1152/physrev.00045.2010.
Physiological processes are strictly organized in space and time. However, in cell physiology research, more attention is given to the question of space rather than to time. To function as a signal, environmental changes must be restricted in time; they need not only be initiated but also terminated. In this review, we concentrate on the role of one specific protein family involved in biological signal termination. GTPase activating proteins (GAPs) accelerate the endogenously low GTP hydrolysis rate of monomeric guanine nucleotide-binding proteins (GNBPs), limiting thereby their prevalence in the active, GTP-bound form. We discuss cases where defective or excessive GAP activity of specific proteins causes significant alteration in the function of the nervous, endocrine, and hemopoietic systems, or contributes to development of infections and tumors. Biochemical and genetic data as well as observations from human pathology support the notion that GAPs represent vital elements in the spatiotemporal fine tuning of physiological processes.
生理过程在空间和时间上都受到严格的调控。然而，在细胞生理学研究中，更多地关注空间问题，而不是时间问题。作为一种信号，环境变化必须在时间上受到限制；它们不仅需要启动，还需要终止。在这篇综述中，我们集中讨论了参与生物信号终止的一个特定蛋白质家族的作用。GTP 酶激活蛋白（GAPs）可加速单体鸟嘌呤核苷酸结合蛋白（GNBPs）的内源低 GTP 水解速率，从而限制其以活性的、GTP 结合形式存在。我们讨论了特定蛋白质的 GAP 活性缺陷或过度会如何导致神经、内分泌和造血系统功能显著改变，或者如何导致感染和肿瘤的发展。生化和遗传数据以及人类病理学观察支持这样一种观点，即 GAPs 是生理过程时空精细调节的重要因素。
