Guanylyl cyclases and signaling by cyclic GMP.
Guanylyl cyclases and signaling by cyclic GMP.
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发表时间：
2000-09
影响因子：
21.1
通讯作者：
Kimberly A. Lucas;G. Pitari;G. Pitari;S. Kazerounian;I. Ruiz-Stewart;Jason Y. Park;S. Schulz;K. Chepenik;S. Waldman
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文献类型：
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作者：
Kimberly A. Lucas;G. Pitari;G. Pitari;S. Kazerounian;I. Ruiz-Stewart;Jason Y. Park;S. Schulz;K. Chepenik;S. Waldman
胍基环化酶是一类催化GTP转化为cGMP的酶。该家族包括几乎在所有细胞类型中表达的膜结合型和可溶性亚型。它们受到多种细胞外激动剂的调节，包括肽激素、细菌毒素和自由基，以及细胞内分子，如钙和腺嘌呤核苷酸。刺激胍基环化酶和由此产生的cGMP积累通过直接下游效应物调节复杂的信号级联反应，包括cGMP依赖的蛋白激酶、cGMP调节的磷酸二酯酶和环核苷酸门控离子通道。胍基环化酶和cgmp介导的信号级联在多种（病理）生理过程的调节中发挥核心作用，包括血管平滑肌运动、肠道液体和电解质稳态以及视网膜光传导。这篇综述的主题包括鸟苷基环化酶基因的结构和染色体定位，鸟苷基环化酶家族成员的结构和功能，调节酶活性的分子机制，以及配体结合催化活性的分子序列。简要概述了由胍基环化酶控制的下游事件，包括受cGMP调节的效应物以及胍基环化酶在细胞生理和病理生理中的作用。
Guanylyl cyclases are a family of enzymes that catalyze the conversion of GTP to cGMP. The family comprises both membrane-bound and soluble isoforms that are expressed in nearly all cell types. They are regulated by diverse extracellular agonists that include peptide hormones, bacterial toxins, and free radicals, as well as intracellular molecules, such as calcium and adenine nucleotides. Stimulation of guanylyl cyclases and the resultant accumulation of cGMP regulates complex signaling cascades through immediate downstream effectors, including cGMP-dependent protein kinases, cGMP-regulated phosphodiesterases, and cyclic nucleotide-gated ion channels. Guanylyl cyclases and cGMP-mediated signaling cascades play a central role in the regulation of diverse (patho)physiological processes, including vascular smooth muscle motility, intestinal fluid and electrolyte homeostasis, and retinal phototransduction. Topics addressed in this review include the structure and chromosomal localization of the genes for guanylyl cyclases, structure and function of the members of the guanylyl cyclase family, molecular mechanisms regulating enzymatic activity, and molecular sequences coupling ligand binding to catalytic activity. A brief overview is presented of the downstream events controlled by guanylyl cyclases, including the effectors that are regulated by cGMP and the role that guanylyl cyclases play in cell physiology and pathophysiology.