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视杆细胞外段膜鸟苷酸环化酶1(ROS-GC1)基因:结构、组织以及蛋白激酶C激活剂佛波酯对其的调控

Rod outer segment membrane guanylate cyclase type 1 (ROS-GC1) gene: structure, organization and regulation by phorbol ester, a protein kinase C activator.

作者信息

Duda T, Venkataraman V, Krishnan A, Sharma R K

机构信息

Department of Cell Biology, University of Medicine and Dentistry of New Jersey, Stratford 08084, USA.

出版信息

Mol Cell Biochem. 1998 Dec;189(1-2):63-70. doi: 10.1023/a:1006944629935.

DOI:10.1023/a:1006944629935
PMID:9879655
Abstract

At present there are two recognized members of the ROS-GC subfamily of membrane guanylate cyclases. They are ROS-GC1 and ROS-GC2. A distinctive feature of this family is that its members are not switched on by the extracellular peptide hormones; instead, they are modulated by intracellular Ca2+ signals, consistent to their linkage with phototransduction. An intriguing feature of ROS-GC1, which distinguishes it from ROS-GC2, is that it has two Ca2+ switches. One switch inhibits the enzyme at micromolar concentrations of Ca2+, as in phototransduction; the other, stimulates. The stimulatory switch, most likely, is linked to retinal synaptic activity. Thus, ROS-GC1 is linked to both phototransduction and the synaptic activity. The present study describes (1) the almost complete structural identity of 18.5 kb ROS-GC1 gene; (2) its structural organization: the gene is composed of 20 exons and 19 introns with classical GT/AG boundaries; (3) the activity of the ROS-GC1 promoter assayed through luciferase reporter in COS cells; and (4) induction of the gene by phorbol ester, a protein kinase C (PKC) activator. The co-presence of PKC and ROS-GC1 in photoreceptors suggests that regulation of the ROS-GC1 gene by PKC might be a physiologically relevant phenomenon.

摘要

目前,膜鸟苷酸环化酶的ROS-GC亚家族有两个公认的成员。它们是ROS-GC1和ROS-GC2。该家族的一个显著特征是其成员不是由细胞外肽激素激活的;相反,它们由细胞内Ca2+信号调节,这与其与光转导的联系一致。ROS-GC1与ROS-GC2的一个有趣区别在于它有两个Ca2+开关。一个开关在微摩尔浓度的Ca2+下抑制该酶,如在光转导中;另一个则起刺激作用。这个刺激开关很可能与视网膜突触活动有关。因此,ROS-GC1与光转导和突触活动都有关联。本研究描述了:(1)18.5 kb的ROS-GC1基因几乎完全的结构一致性;(2)其结构组织:该基因由20个外显子和19个内含子组成,具有经典的GT/AG边界;(3)通过荧光素酶报告基因在COS细胞中检测ROS-GC1启动子的活性;(4)佛波酯(一种蛋白激酶C(PKC)激活剂)对该基因的诱导作用。PKC和ROS-GC1在光感受器中的共同存在表明PKC对ROS-GC1基因的调节可能是一种生理相关现象。

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