Department of Nephrology, The Second Xiangya Hospital, Kidney Institute of Nephrology, Central South University, Changsha, Hunan Province, China.
Am J Physiol Renal Physiol. 2013 Apr 1;304(7):F831-9. doi: 10.1152/ajprenal.00711.2012. Epub 2013 Jan 30.
Exchange proteins directly activated by cAMP [Epac(s)] were discovered more than a decade ago as new sensors for the second messenger cAMP. The Epac family members, including Epac1 and Epac2, are guanine nucleotide exchange factors for the Ras-like small GTPases Rap1 and Rap2, and they function independently of protein kinase A. Given the importance of cAMP in kidney homeostasis, several molecular and cellular studies using specific Epac agonists have analyzed the role and regulation of Epac proteins in renal physiology and pathophysiology. The specificity of the functions of Epac proteins may depend upon their expression and localization in the kidney as well as their abundance in the microcellular environment. This review discusses recent literature data concerning the involvement of Epac in renal tubular transport physiology and renal glomerular cells where various signaling pathways are known to be operative. In addition, the potential role of Epac in kidney disorders, such as diabetic kidney disease and ischemic kidney injury, is discussed.
十多年前，人们发现环腺苷酸（cAMP）直接激活的交换蛋白[Epac（s）]是 cAMP 这种第二信使的新型传感器。Epac 家族成员包括 Epac1 和 Epac2，是 Ras 样小分子 GTP 酶 Rap1 和 Rap2 的鸟嘌呤核苷酸交换因子，它们独立于蛋白激酶 A 发挥作用。鉴于 cAMP 在肾脏稳态中的重要性，使用特定 Epac 激动剂的几种分子和细胞研究分析了 Epac 蛋白在肾脏生理学和病理生理学中的作用和调节。Epac 蛋白功能的特异性可能取决于它们在肾脏中的表达和定位以及它们在微环境中的丰度。本文综述了有关 Epac 参与肾小管转运生理学和肾脏肾小球细胞的最新文献数据，其中已知存在各种信号通路。此外，还讨论了 Epac 在肾脏疾病（如糖尿病肾病和缺血性肾损伤）中的潜在作用。
