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编码PDE5A(一种人源cGMP结合的、cGMP特异性3',5'-环核苷酸磷酸二酯酶)的cDNA的分离与鉴定

Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase.

作者信息

Loughney K, Hill T R, Florio V A, Uher L, Rosman G J, Wolda S L, Jones B A, Howard M L, McAllister-Lucas L M, Sonnenburg W K, Francis S H, Corbin J D, Beavo J A, Ferguson K

机构信息

ICOS Corporation, Bothell, WA 98021, USA.

出版信息

Gene. 1998 Aug 17;216(1):139-47. doi: 10.1016/s0378-1119(98)00303-5.

Abstract

Human cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase (PDE5A) cDNAs were isolated. A 3.1-kb composite DNA sequence assembled from overlapping cDNAs encodes an 875-amino-acid protein with a predicted molecular mass of 100012 Da (PDE5A1). Extracts prepared from yeast expressing human PDE5A1 hydrolyzed cGMP. This activity was inhibited by the selective PDE5 inhibitors zaprinast and DMPPO. PDE5A mRNA is expressed in aortic smooth muscle cells, heart, placenta, skeletal muscle and pancreas and, to a much lesser extent, in brain, liver and lung. A 5'-splice variant, PDE5A2, encodes an 833-amino-acid protein with eight unique amino acids at the amino terminus. PDE5A maps to chromosome 4q 25-27.

摘要

人源环磷酸鸟苷(cGMP)结合的、cGMP特异性3',5'-环核苷酸磷酸二酯酶(PDE5A)的互补DNA(cDNA)被分离出来。由重叠cDNA组装而成的一个3.1千碱基对的复合DNA序列编码一个875个氨基酸的蛋白质,预测分子量为100012道尔顿(PDE5A1)。从表达人PDE5A1的酵母中制备的提取物可水解cGMP。这种活性受到选择性PDE5抑制剂扎普司特和DMPPO的抑制。PDE5A信使核糖核酸(mRNA)在主动脉平滑肌细胞、心脏、胎盘、骨骼肌和胰腺中表达,而在脑、肝和肺中的表达程度要低得多。一个5'-剪接变体PDE5A2编码一个在氨基末端有八个独特氨基酸的833个氨基酸的蛋白质。PDE5A定位于4号染色体的q25-27区域。

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