Protein-protein interactions involving inducible nitric oxide synthase.
Protein-protein interactions involving inducible nitric oxide synthase.
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DOI：
10.1046/j.1365-201x.2003.01119.x
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发表时间：
2003-10
期刊：
影响因子：
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通讯作者：
Wenzheng Zhang;T. Kuncewicz;Zhi Yuan Yu;Lei Zou;X. Xu;Bruce C. Kone
中科院分区：
文献类型：
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作者：
Wenzheng Zhang;T. Kuncewicz;Zhi Yuan Yu;Lei Zou;X. Xu;Bruce C. Kone
AIM 一氧化氮 (NO) 是一种信号传导和效应分子，有助于肾脏、脉管系统和其他组织的多种生理和病理生理过程。诱导型一氧化氮合酶 (iNOS) 产生的高输出一氧化氮参与宿主对病原体的防御，并在炎症状态下导致组织损伤。由于其强大的反应性和扩散性，iNOS 生成的 NO 受到多个层面的调控，包括转录、翻译和翻译后控制，包括蛋白质-蛋白质相互作用。本综述探讨了这些蛋白质-蛋白质相互作用的实验基础及其对肾脏和血管生理学的已知和潜在重要性。方法 分析该领域的生物医学文献。结果 iNOS 与抑制分子 Kalirin 和 NOS 相关蛋白 1.10 kd (NAP110) 相互作用，抑制 iNOS 同二聚化，以及激活蛋白 Rac-GTP 酶。与 Caveolin-1 的相互作用控制肿瘤细胞中 iNOS 的细胞内区域和降解。在极化上皮细胞中，iNOS 与支架蛋白 EBP50 的结合将 iNOS 定位在顶膜中靠近关键离子转运蛋白的位置，这些离子转运蛋白也与 EPB50 相互作用。此外，控制 iNOS 转录的蛋白质之间的蛋白质-蛋白质相互作用可指定细胞因子对 iNOS 诱导的激活或抑制。结论 iNOS 与多种异源蛋白的相互作用提供了一种选择性机制来控制 iNOS 的活性、空间分布和与预期靶标的接近度，同时可能限制对 iNOS 表达细胞的自毒性。
AIM Nitric oxide (NO) is a signaling and effector molecule that contributes to multiple physiological and pathophysiological processes in the kidney, vasculature, and other tissues. High output NO generation by inducible NO synthase (iNOS) participates in host defense against pathogens and contributes to tissue injury during inflammatory states. Because of its potent reactivity and diffusibility, NO generation by iNOS is subject to multiple levels of regulation, including transcriptional, translational, and post-translational controls, including protein-protein interactions. This review examines the experimental basis for these protein-protein interactions and their known and potential importance for kidney and vascular physiology. METHODS Analysis of the biomedical literature in the area. RESULTS iNOS interacts with the inhibitory molecules Kalirin and NOS-associated protein 1.10 kd (NAP110), which inhibit iNOS homodimerization, as well as activator proteins, the Rac-GTPases. Interactions with caveolin-1 control the intracellular locale and degradation of iNOS in tumor cells. In polarized epithelial cells, associations of iNOS with the scaffolding protein EBP50 position iNOS in the apical membrane near key ion transport proteins that also interact with EPB50. In addition, protein-protein interactions of proteins governing iNOS transcription function to specify activation or suppression of iNOS induction by cytokines. CONCLUSION Interactions of iNOS with a diverse group of heterologous proteins provides a selective mechanism to control the activity, spatial distribution, and proximity of iNOS to intended targets, while potentially limiting autotoxicity to the iNOS-expressing cell.