A novel calcium-dependent activator of retinal rod outer segment membrane guanylate cyclase.
A novel calcium-dependent activator of retinal rod outer segment membrane guanylate cyclase.
复制标题
一种新型钙依赖性视网膜杆外节膜鸟苷酸环化酶激活剂。
DOI：
10.1021/bi00044a002
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发表时间：
1995
期刊：
影响因子：
2.9
通讯作者：
Sitaramayya,A
中科院分区：
文献类型：
--
作者：
Pozdnyakov,N;Yoshida,A;Cooper,NG;Margulis,A;Duda,T;Sharma,RK;Sitaramayya,A
收到修订稿1995年9月19日®摘要：已知视网膜视杆外节（ROS-GC）中的膜鸟苷酸环化酶受到钙的负调节;当钙浓度降低至暗适应水平（约500 nM）以下时，该酶被可溶性蛋白质激活。我们现在报告说，该酶也正调控钙;一种新的可溶性蛋白质被确定和纯化的牛视网膜激活ROS-GC，半最大激活发生在2-5 pM钙。激活是剂量依赖性的，在其最大值，环化酶被刺激高达25倍。鸟苷酸环化酶（GC）是一种分子量约为40 kDa的多肽多聚体，催化GTP生成环鸟苷酸。可溶性和膜相关的环化酶活性在几种组织中都有发现（Kimura & Murad，1974）。在其调节机制已知的膜相关环化酶中，可以根据调节其活性的肽鉴定出两组。一组成员，通常称为受体（Schultz等人，1989; Sharma等人，1994; Garbers & Lowe，1994）由推测与其细胞外结构域结合的肽调节。这些包括在几种组织中作为利钠激素受体的环化酶，由鸟苷酸或热稳定肠毒素激活的肠环化酶，由卵肽如resact和speract激活的海胆精子环化酶，以及其他肽激素调节的酶。另一组中的膜相关酶没有任何已知的激素调节剂，但被胞质蛋白激活。这些包括
Revised Manuscript ReceivedSeptember 19, 1995® abstract: The membrane guanylate cyclase in retinal rod outer segments (ROS-GC) is known to be negatively regulated by calcium; when the calcium concentration is reduced below the dark-adapted level of about 500 nM, the enzyme is activated by a soluble protein. We now report that the enzyme is also positively regulated by calcium; a novel soluble protein is identified and purified from bovine retina which activates ROS-GC, with half-maximal activation occurring at 2—5 pM calcium. The activation is dose-dependent, and at its maximum, cyclase is stimulated up to 25-fold. The activator has a molecular mass of about 40 kDa and is a multimer of a 6—7 kDa peptide.Guanylate cyclase (GC) catalyzes the formation of cyclic GMP from GTP. Both soluble and membrane-associated cyclase activities are found in severaltissues (Kimura & Murad, 1974). Of the membrane-associated cyclases whose mechanism of regulation is known, two groups can be identified on the basis of the peptides regulating theiractivity. Members of one group, often referred to as receptors (Schultz et al., 1989; Sharma et al., 1994; Garbers & Lowe, 1994), are regulated by peptides presumably binding to their extracellular domains. These include cyclases in several tissues serving as receptors for natriuretic hormones, the intestinal cyclase activated by guanylins or heat-stable enterotoxins, sea urchin sperm cyclase activated by egg peptides such as resact and speract, and other peptide-hormone-regulated enzymes. Membrane-associated enzymes in the other group do not have any known hormone regulators but are activated by cytosolic proteins. These include