Roscioni Sara S, Elzinga Carolina R S, Schmidt Martina
Department of Molecular Pharmacology, University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Naunyn Schmiedebergs Arch Pharmacol. 2008 Jun;377(4-6):345-57. doi: 10.1007/s00210-007-0246-7. Epub 2008 Jan 5.
Epac1 (also known as cAMP-GEF-I) and Epac2 (also known as cAMP-GEF-II) are cyclic AMP-activated guanine nucleotide exchange factors for Ras-like GTPases. Since their discovery about 10 years ago, it is now accepted that Epac proteins are novel cAMP sensors that regulate several pivotal cellular processes, including calcium handling, cell proliferation, cell survival, cell differentiation, cell polarization, cell-cell adhesion events, gene transcription, secretion, ion transport, and neuronal signaling. Recent studies even indicated that Epac proteins might play a role in the regulation of inflammation and the development of cardiac hypertrophy. Meanwhile, a plethora of diverse effectors of Epac proteins have been assigned, such as Ras and Rho GTPases, phospholiase C-epsilon, phospholipase D, mitogen-activated protein kinases, protein kinase B/Akt, ion channels, secretory-granule associated proteins and regulators of the actin-microtubule network, the latter probably involved in the spatiotemporal dynamics of Epac-related signaling. This review highlights multi-faceted effectors and diverse biological functions driven by Epac proteins that might explain certain controversial signaling properties of cAMP.
Epac1（也称为cAMP-GEF-I）和Epac2（也称为cAMP-GEF-II）是Ras样GTP酶的环磷酸腺苷（cAMP）激活的鸟嘌呤核苷酸交换因子。自从大约10年前被发现以来，现在人们公认Epac蛋白是新型的cAMP传感器，可调节多个关键的细胞过程，包括钙处理、细胞增殖、细胞存活、细胞分化、细胞极化、细胞间黏附事件、基因转录、分泌、离子转运和神经元信号传导。最近的研究甚至表明，Epac蛋白可能在炎症调节和心脏肥大的发展中起作用。同时，Epac蛋白已被确定有大量不同的效应器，如Ras和Rho GTP酶、磷脂酶C-ε、磷脂酶D、丝裂原活化蛋白激酶、蛋白激酶B/Akt、离子通道、分泌颗粒相关蛋白以及肌动蛋白-微管网络的调节剂，后者可能参与Epac相关信号传导的时空动态。本综述重点介绍了由Epac蛋白驱动的多方面效应器和多样的生物学功能，这可能解释了cAMP某些有争议的信号特性。
