Duda T, Goraczniak R M, Sitaramayya A, Sharma R K
Unit of Regulatory and Molecular Biology, Pennsylvania College of Optometry, Philadelphia 19141.
Biochemistry. 1993 Feb 16;32(6):1391-5. doi: 10.1021/bi00057a001.
The natriuretic factors are structurally related polypeptide hormones that regulate the hemodynamics of the physiological processes of diuresis, water balance, and blood pressure. Presumably, these hormones act through the activation of guanylate cyclases which are also the specific receptors of these hormones. Two such structurally similar cell surface receptors are known; the ligand for one is atrial natriuretic factor (ANF) and for the other is C-type natriuretic peptide (CNP). Studies with ANF receptor guanylate cyclase (ANF-RGC) have indicated that its ligand binding site is extracellular and the catalytic site is intracellular, but the mere ligand binding to the receptor domain does not activate the cytosolic catalytic domain. An intervening ATP-mediated event is obligatory: ATP binds to a defined ATP-regulated module (ARM) sequence and bridges the events of ligand binding and signal transduction. The mechanism of CNP signaling is not known, although CNP in intact cells transfected with CNP receptor guanylate cyclase (CNP-RGC) stimulates the formation of cyclic GMP. Furthermore, there is no prior evidence of the presence of CNP signal transduction system in retina, although the presence of ANF-RGC has been documented. We now report the molecular cloning and expression of CNP-RGC from human retina and show that ATP is obligatory in CNP signaling also.(ABSTRACT TRUNCATED AT 250 WORDS)
利钠因子是结构相关的多肽激素，可调节利尿、水平衡和血压等生理过程的血流动力学。据推测，这些激素通过激活鸟苷酸环化酶起作用，而鸟苷酸环化酶也是这些激素的特异性受体。已知有两种结构相似的细胞表面受体；一种的配体是心房利钠因子（ANF），另一种的配体是C型利钠肽（CNP）。对ANF受体鸟苷酸环化酶（ANF-RGC）的研究表明，其配体结合位点在细胞外，催化位点在细胞内，但仅仅配体与受体结构域结合并不能激活胞质催化结构域。一个中间的ATP介导事件是必需的：ATP与一个确定的ATP调节模块（ARM）序列结合，并在配体结合和信号转导事件之间起桥梁作用。尽管在转染了CNP受体鸟苷酸环化酶（CNP-RGC）的完整细胞中CNP会刺激环磷酸鸟苷的形成，但CNP信号传导的机制尚不清楚。此外，尽管已经记录了ANF-RGC在视网膜中的存在，但之前没有证据表明视网膜中存在CNP信号转导系统。我们现在报告从人视网膜中克隆和表达CNP-RGC，并表明ATP在CNP信号传导中也是必需的。（摘要截短于250字）
