Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, United States of America.
PLoS One. 2011 Jan 20;6(1):e16039. doi: 10.1371/journal.pone.0016039.
Differential expression of proteins between tissues underlies organ-specific functions. Under certain pathological conditions, this may also lead to tissue vulnerability. Furthermore, post-translational modifications exist between different cell types and pathological conditions. We employed SILAM (Stable Isotope Labeling in Mammals) combined with mass spectrometry to quantify the proteome between mammalian tissues. Using (15)N labeled rat tissue, we quantified 3742 phosphorylated peptides in nuclear extracts from liver and brain tissue. Analysis of the phosphorylation sites revealed tissue specific kinase motifs. Although these tissues are quite different in their composition and function, more than 500 protein identifications were common to both tissues. Specifically, we identified an up-regulation in the brain of the phosphoprotein, ZFHX1B, in which a genetic deletion causes the neurological disorder Mowat-Wilson syndrome. Finally, pathway analysis revealed distinct nuclear pathways enriched in each tissue. Our findings provide a valuable resource as a starting point for further understanding of tissue specific gene regulation and demonstrate SILAM as a useful strategy for the differential proteomic analysis of mammalian tissues.
蛋白质在组织间的差异表达是器官特异性功能的基础。在某些病理条件下，这也可能导致组织脆弱。此外，不同细胞类型和病理条件之间存在翻译后修饰。我们采用 SILAM（哺乳动物中的稳定同位素标记）结合质谱技术来定量哺乳动物组织之间的蛋白质组。使用（15）N 标记的大鼠组织，我们定量了来自肝和脑组织核提取物中的 3742 个磷酸化肽。磷酸化位点的分析揭示了组织特异性激酶基序。尽管这些组织在组成和功能上有很大的不同，但有超过 500 种蛋白质在这两种组织中都被鉴定出来。具体来说，我们在大脑中发现了磷酸化蛋白 ZFHX1B 的上调，其遗传缺失会导致神经障碍 Mowat-Wilson 综合征。最后，通路分析显示每个组织中都富含独特的核通路。我们的发现为进一步了解组织特异性基因调控提供了有价值的资源，并证明 SILAM 是用于哺乳动物组织差异蛋白质组分析的有用策略。
