Epithelial Systems Biology Laboratory, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA.
Expert Rev Proteomics. 2011 Apr;8(2):157-63. doi: 10.1586/epr.11.14.
Protein phosphorylation plays a critical role in the signaling pathways regulating water and solute transport in the distal renal tubule (i.e., renal collecting duct). A central mediator in this process is the antidiuretic peptide hormone arginine vasopressin, which regulates a number of transport proteins including water channel aquaporin-2 and urea transporters (UT-A1 and UT-A3). Within the past few years, tandem mass spectrometry-based proteomics has played a pivotal role in revealing global changes in the phosphoproteome in response to vasopressin signaling in the renal collecting duct. This type of large-scale 'shotgun' approach has resulted in an exponential increase in the number of phosphoproteins known to be regulated by vasopressin and has expanded on the established signaling mechanisms and kinase pathways regulating collecting duct physiology. This article will provide a brief background on vasopressin action, will highlight a number of recent quantitative phosphoproteomic studies in both native rat kidney and cultured collecting duct cells, and will conclude with a perspective focused on emerging trends in the field of phosphoproteomics.
蛋白质磷酸化在调节远曲肾小管(即肾集合管)中水分和溶质转运的信号通路中起着关键作用。这一过程的一个核心介质是抗利尿肽激素血管加压素,它调节包括水通道 aquaporin-2 和尿素转运蛋白(UT-A1 和 UT-A3)在内的许多转运蛋白。在过去的几年中,基于串联质谱的蛋白质组学在揭示肾集合管中血管加压素信号对磷酸蛋白质组的全球变化方面发挥了关键作用。这种大规模的“鸟枪法”方法导致了受血管加压素调节的磷酸化蛋白数量呈指数级增长,并扩展了已建立的调节集合管生理学的信号转导机制和激酶途径。本文将简要介绍血管加压素的作用,重点介绍一些最近在天然大鼠肾脏和培养的集合管细胞中进行的定量磷酸蛋白质组学研究,并以聚焦于磷酸蛋白质组学领域新兴趋势的观点作为结论。