编码一种受环磷酸鸟苷（cGMP）刺激的3',5'-环核苷酸磷酸二酯酶的人类互补DNA（cDNA）的分离与特性鉴定

Isolation and characterization of human cDNAs encoding a cGMP-stimulated 3',5'-cyclic nucleotide phosphodiesterase.

作者信息

Rosman G J, Martins T J, Sonnenburg W K, Beavo J A, Ferguson K, Loughney K

机构信息

ICOS Corporation, Bothell, WA 98201, USA.

出版信息

Gene. 1997 May 20;191(1):89-95. doi: 10.1016/s0378-1119(97)00046-2.

DOI:10.1016/s0378-1119(97)00046-2

PMID:9210593

Abstract

Human cyclic GMP-stimulated 3',5'-cyclic nucleotide phosphodiesterase (PDE2A3) cDNAs were cloned from hippocampus and fetal brain cDNA libraries. A 4.2-kb composite DNA sequence constructed from overlapping cDNA clones encodes a 941 amino acid protein with a predicted molecular mass of 105,715 Da. Extracts prepared from yeast expressing the human PDE2A3 hydrolyzed both cyclic AMP (cAMP) and cyclic GMP (cGMP). This activity was inhibited by EHNA, a selective PDE2 inhibitor, and was stimulated three-fold by cGMP. Human PDE2A is expressed in brain and to a lesser extent in heart, placenta, lung, skeletal muscle, kidney and pancreas. The human PDE2A3 differs from the bovine PDE2A1 and rat PDE2A2 proteins at the amino terminus but its amino-terminal sequence is identical to the bovine PDE2A3 sequence. The different amino termini probably arise from alternative exon splicing of the PDE2A mRNA.

摘要

人环鸟苷酸刺激的3',5'-环核苷酸磷酸二酯酶（PDE2A3）的互补DNA（cDNA）从海马和胎儿脑cDNA文库中克隆得到。由重叠的cDNA克隆构建的一个4.2千碱基对的复合DNA序列编码一个含941个氨基酸的蛋白质，预测分子量为105,715道尔顿。从表达人PDE2A3的酵母制备的提取物能水解环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）。这种活性受到选择性PDE2抑制剂EHNA的抑制，并被cGMP刺激3倍。人PDE2A在脑中表达，在心脏、胎盘、肺、骨骼肌、肾脏和胰腺中表达程度较低。人PDE2A3在氨基末端与牛PDE2A1和大鼠PDE2A2蛋白不同，但其氨基末端序列与牛PDE2A3序列相同。不同的氨基末端可能源于PDE2A信使核糖核酸（mRNA）的选择性外显子剪接。