Francis S H, Turko I V, Corbin J D
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Prog Nucleic Acid Res Mol Biol. 2001;65:1-52. doi: 10.1016/s0079-6603(00)65001-8.
Cyclic nucleotide phosphodiesterases (PDEs) comprise a superfamily of metallophosphohydrolases that specifically cleave the 3',5'-cyclic phosphate moiety of cAMP and/or cGMP to produce the corresponding 5'-nucleotide. PDEs are critical determinants for modulation of cellular levels of cAMP and/or cGMP by many stimuli. Eleven families of PDEs with varying selectivities for cAMP or cGMP have been identified in mammalian tissues. Within these families, multiple isoforms are expressed either as products of different genes or as products of the same gene through alternative splicing. Regulation of PDEs is important for controlling myriad physiological functions, including the visual response, smooth muscle relaxation, platelet aggregation, fluid homeostasis, immune responses, and cardiac contractility. PDEs are critically involved in feedback control of cellular cAMP and cGMP levels. Activities of the various PDEs are highly regulated by a panoply of processes, including phosphorylation events, interaction with small molecules such as cGMP or phosphatidic acid, subcellular localization, and association with specific protein partners. The PDE superfamily continues to be a major target for pharmacological intervention in a number of medically important maladies.
环核苷酸磷酸二酯酶（PDEs）是金属磷酸水解酶的一个超家族，它特异性地切割cAMP和/或cGMP的3',5'-环磷酸部分，生成相应的5'-核苷酸。PDEs是许多刺激调节细胞内cAMP和/或cGMP水平的关键决定因素。在哺乳动物组织中已鉴定出11个对cAMP或cGMP具有不同选择性的PDEs家族。在这些家族中，多种亚型通过不同基因的产物或同一基因通过可变剪接的产物来表达。PDEs的调节对于控制无数生理功能很重要，包括视觉反应、平滑肌舒张、血小板聚集、液体平衡、免疫反应和心脏收缩力。PDEs在细胞cAMP和cGMP水平的反馈控制中起关键作用。各种PDEs的活性受到一系列过程的高度调节，包括磷酸化事件、与小分子如cGMP或磷脂酸的相互作用、亚细胞定位以及与特定蛋白质伴侣的结合。PDE超家族仍然是许多医学上重要疾病药物干预的主要靶点。
