Phosphoproteins with stability against all urinary phosphatases as potential biomarkers
- Published
- Accepted
- Subject Areas
- Biochemistry
- Keywords
- Urine proteome, Phosphoproteins, Biomarkers
- Copyright
- © 2014 Zhao et al.
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ PrePrints) and either DOI or URL of the article must be cited.
- Cite this article
- 2014. Phosphoproteins with stability against all urinary phosphatases as potential biomarkers. PeerJ PrePrints 2:e728v1 https://doi.org/10.7287/peerj.preprints.728v1
Abstract
Urine, by accumulating all kinds of changes, was proposed to be a better source for biomarker discovery. As one of the most common post-translational modifications, phosphorylation plays a vital role in many biological activities. However, the urine phosphoproteome has been largely neglected due to the low abundance of phosphoproteins and the presence of various phosphatases in urine. The low level of background phosphorylation in urine is actually advantageous, as urinary phosphopeptides/proteins that are stable to the phosphatases present in urine have the potential to serve as valuable disease biomarkers. Using a TiO2 enrichment strategy, this study aimed to create a comprehensive proteomic profile of human urinary phosphoproteins and to characterize the changes in the urine phosphoproteome after incubation of urine with cell lysates. In total, 106 urine phosphorylation sites corresponding to 64 proteins, including 80 previously unidentified human urine protein phosphorylation sites, were identified by mass spectrometry. Fifteen phosphopeptides, together averaging 47% of the total phosphopeptides, were found in samples from three individuals. Addition of cellular proteins to urine did not significantly change the phosphorylation level of urine proteins. But there were still a few phosphopeptides from cell lysates survived urinary phosphatases; such phosphopeptides represent potential biomarkers in urine.
Author Comment
This is a submission to PeerJ for review. Realization and emphasis of change as the most fundamental property of biomarker, urine, by accumulating all kinds of changes, was proposed to be a better source for biomarker discovery. The urine proteome has been commonly used in discovering biomarkers of renal, bladder and prostate diseases. As one of the most common post-translational modifications, phosphorylation play vital roles in many biological activities. However, the urine phosphoproteome has been largely neglected due to the low abundance of phosphoproteins and the presence of various phosphatases in urine. But we believe the low level of background phosphorylation in urine is actually advantageous, as urinary phosphopeptides and proteins that are able to survive the phosphatases present in urine can potentially serve as valuable disease biomarkers.
