Early Detection Research Network

Mapping tissue-specific expression of extracellular proteins using systematic glycoproteomic analysis of different mouse tissues.

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 them 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.

Kelly-Spratt KS, Kemp CJ, Tian Y, Zhang H

20828161

J. Proteome Res., 2010, 9 (11)

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