Department of Integrative Biology and Pharmacology, Texas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center , Houston, Texas.
Physiol Rev. 2018 Apr 1;98(2):919-1053. doi: 10.1152/physrev.00025.2017.
This review focuses on one family of the known cAMP receptors, the exchange proteins directly activated by cAMP (EPACs), also known as the cAMP-regulated guanine nucleotide exchange factors (cAMP-GEFs). Although EPAC proteins are fairly new additions to the growing list of cAMP effectors, and relatively "young" in the cAMP discovery timeline, the significance of an EPAC presence in different cell systems is extraordinary. The study of EPACs has considerably expanded the diversity and adaptive nature of cAMP signaling associated with numerous physiological and pathophysiological responses. This review comprehensively covers EPAC protein functions at the molecular, cellular, physiological, and pathophysiological levels; and in turn, the applications of employing EPAC-based biosensors as detection tools for dissecting cAMP signaling and the implications for targeting EPAC proteins for therapeutic development are also discussed.
这篇综述集中讨论了已知 cAMP 受体家族中的一个家族，即 cAMP 直接激活的交换蛋白（EPAC），也称为 cAMP 调节的鸟苷酸交换因子（cAMP-GEFs）。尽管 EPAC 蛋白是不断增长的 cAMP 效应物列表中的新增成员，并且在 cAMP 发现时间轴上相对“年轻”，但它们在不同细胞系统中的存在意义非凡。对 EPAC 的研究极大地扩展了与许多生理和病理生理反应相关的 cAMP 信号的多样性和适应性。本综述全面涵盖了 EPAC 蛋白在分子、细胞、生理和病理生理水平上的功能；反过来，也讨论了基于 EPAC 的生物传感器作为用于剖析 cAMP 信号的检测工具的应用，以及针对 EPAC 蛋白进行治疗开发的意义。
