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人类9型腺苷酸环化酶(ADCY9)的克隆、染色体定位及调控特性

Cloning, chromosomal mapping, and regulatory properties of the human type 9 adenylyl cyclase (ADCY9).

作者信息

Hacker B M, Tomlinson J E, Wayman G A, Sultana R, Chan G, Villacres E, Disteche C, Storm D R

机构信息

Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA.

出版信息

Genomics. 1998 May 15;50(1):97-104. doi: 10.1006/geno.1998.5293.

DOI:10.1006/geno.1998.5293
PMID:9628827
Abstract

The type 9 adenylyl cyclase (AC9) is a widely distributed adenylyl cyclase that was originally cloned from a mouse cDNA library. Here we report the cloning, chromosomal mapping, and regulatory properties of human AC9 (HGMW-approved symbol ADCY9). Although the human AC9 sequence shows 86% homology with mouse AC9, divergence at the C2a/C2b junction results in an alternative C2b amino acid sequence. In situ hybridization localized the human AC9 gene to both human and mouse chromosomes 16. AC9 mRNA is present in all tissues examined, with the highest levels found in skeletal muscle, heart, and brain. To characterize the regulatory properties of human AC9 in vivo, the enzyme was expressed in HEK-293 cells. Human AC9 is stimulated by beta-adrenergic receptor activation but is insensitive to forskolin, Ca2+ and somatostatin. In contrast to mouse AC9, the activity of human AC9 is unaffected by inhibitors of calcineurin. These data emphasize the importance of determining the regulatory properties of human adenylyl cyclases.

摘要

9型腺苷酸环化酶(AC9)是一种广泛分布的腺苷酸环化酶,最初是从小鼠cDNA文库中克隆出来的。在此,我们报告人类AC9(HGMW批准符号ADCY9)的克隆、染色体定位及调节特性。尽管人类AC9序列与小鼠AC9有86%的同源性,但C2a/C2b连接处的差异导致了C2b氨基酸序列的不同。原位杂交将人类AC9基因定位到人类和小鼠的16号染色体上。在所检测的所有组织中均存在AC9 mRNA,其中在骨骼肌、心脏和大脑中的水平最高。为了在体内表征人类AC9的调节特性,该酶在HEK-293细胞中表达。人类AC9受β-肾上腺素能受体激活的刺激,但对福斯可林、Ca2+和生长抑素不敏感。与小鼠AC9不同,人类AC9的活性不受钙调神经磷酸酶抑制剂的影响。这些数据强调了确定人类腺苷酸环化酶调节特性的重要性。

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