Abstract
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 15N 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.
Highlights
A puzzling phenomenon in many neurological diseases is that mutations in individual genes cause neurological specific phenotypes, but the genes are ubiquitously expressed throughout the body
methyl-CpGbinding protein 2 (MECP2) is ubiquitously expressed, it has been demonstrated that it is phosphorylated at S421 only in the brain, and this neuronal specific phosphorylation event leads to the transcription of brainderived neurotrophic factor (BDNF) [5], which is crucial for neuronal cell development and neural circuits formation
This MECP2 study is a breakthrough in the role of phosphorylation in neurological disease, it is tempting to speculate that other phosphorylation events might happen in MECP2 as well as other master regulatory proteins during cell differentiation and tissue development that contribute to pleiotropic functions
Summary
A puzzling phenomenon in many neurological diseases is that mutations in individual genes cause neurological specific phenotypes, but the genes are ubiquitously expressed throughout the body. MECP2 is ubiquitously expressed, it has been demonstrated that it is phosphorylated at S421 only in the brain, and this neuronal specific phosphorylation event leads to the transcription of brainderived neurotrophic factor (BDNF) [5], which is crucial for neuronal cell development and neural circuits formation. This MECP2 study is a breakthrough in the role of phosphorylation in neurological disease, it is tempting to speculate that other phosphorylation events might happen in MECP2 as well as other master regulatory proteins during cell differentiation and tissue development that contribute to pleiotropic functions. There has been no quantitative large-scale analysis of the phosphorylation differences between the brain and other mammalian tissues
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