Mapping tissue-specific expression of extracellular proteins using systematic glycoproteomic analysis of different mouse tissues.
Mapping tissue-specific expression of extracellular proteins using systematic glycoproteomic analysis of different mouse tissues.
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DOI：
10.1021/pr1006075
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发表时间：
2010-11-05
影响因子：
4.4
通讯作者：
Zhang, Hui
中科院分区：
文献类型：
--
作者：
Tian, Yuan;Kelly-Spratt, Karen S.;Kemp, Christopher J.;Zhang, Hui
关键词：
由于其易于获得，质膜外的蛋白质代表了潜在药物靶点或疾病生物标志物的理想但未开发的资源。它们构成了目前治疗靶点和临床生物标志物的主要生化类别。蛋白质组学技术的最新进展激发了对细胞外蛋白质如膜蛋白、细胞表面蛋白和分泌蛋白的分析的兴趣。然而，与使用基因组技术从多种组织和细胞中进行基因表达分析不同，由于不同蛋白质组的高度复杂性，以及缺乏用于分析不同组织来源的稳健和一致的方法，特别是用于细胞外蛋白质的特异性富集，来自各种生物来源的蛋白质的定量蛋白质组学分析是具有挑战性的。由于大多数细胞外蛋白被寡糖修饰，因此糖蛋白群体代表了大多数细胞外蛋白质组。在这里，我们定量分析糖蛋白，并确定了12个小鼠组织的胞外蛋白的表达模式，使用固相萃取的N-连接的糖肽和液相色谱串联质谱。我们从826种独特的蛋白质中鉴定出1231种可能的N-连接糖基的肽。我们进一步确定了以前的N-连接的糖肽的表达模式，并确定了在每个组织中特异性表达的胞外糖蛋白。此外，通过比较不同组织的蛋白质定量表达来确定小鼠皮肤肿瘤模型中过表达糖蛋白的组织特异性。这些皮肤肿瘤特异性细胞外蛋白可能作为细胞表面药物靶点或疾病特异性蛋白标志物的潜在候选者。
Due to their easy accessibility, proteins outside of the plasma membrane represent an ideal but untapped resource for potential drug targets or disease biomarkers. They constitute the major biochemical class of current therapeutic targets and clinical biomarkers. Recent advances in proteomic technologies have fueled interest in analysis of extracellular proteins such as membrane proteins, cell surface proteins, and secreted proteins. However, unlike the gene expression analyses from a variety of tissues and cells using genomic technologies, quantitative proteomic analysis of proteins from various biological sources is challenging due to the high complexity of different proteomes, and the lack of robust and consistent methods for analyses of different tissue sources, especially for specific enrichment of extracellular proteins. Since most extracellular proteins are modified by oligosaccharides, the population of glycoproteins therefore represents the majority of extracellular proteomes. Here, we quantitatively analyzed glycoproteins and determined the expression patterns of extracellular proteins from 12 mouse tissues using solid-phase extraction of N-linked glycopeptides and liquid chromatography tandem mass spectrometry. We identified peptides enclosing 1231 possible N-linked glycosites from 826 unique proteins. We further determined the expression pattern of formerly N-linked glycopeptides and identified extracellular glycoproteins specifically expressed in each tissue. Furthermore, the tissue specificities of the overexpressed glycoproteins in a mouse skin tumor model were determined by comparing to the quantitative protein expression from the different tissues. These skin tumor-specific extracellular proteins might serve as potential candidates for cell surface drug targets or disease-specific protein markers.
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