Editorial pubs.acs.org/ac
Phosphoproteomics §
M
uch of the communication within, and in between, cells proceeds via a variety of (dynamic) covalent protein modifications. One of the most abundant, and important, modifications to proteins is phosphorylation. Enzymes called kinases and phosphatases add and remove phosphate to proteins, respectively. The exquisite specificity of phosphorylation reactions creates regulatory and signaling processes within cells by changes in phosphorylation along pathways and/ or networks of proteins. A challenge in cell biology is deciphering the sites of phosphorylation in proteins as well as the dynamics of the reaction and the location of the modification within the cell. The analytical challenge of deciphering protein phosphorylation is great as the presence of phosphorylation first needs to be detected and then the site of phosphorylation within a protein needs to be determined. The first methods for analysis of phosphorylation used paper electrochromatography, amino acid analysis, and Edman degradation. In the 1980s, mass spectrometry emerged as a powerful method for the analysis of phosphopeptides, but it gained popularity as a proteomic method with the development of efficient phosphopeptide enrichment methods and, perhaps more significantly, when automated methods were developed to interpret the large-scale mass spectrometry data and identify phosphorylation sites. Phosphoproteomics is more complicated than simply measuring protein expression, as the stoichiometry of phosphorylation is often low and clearly and accurately determining the site of phosphorylation is key to understanding signaling pathways and enzyme regulation. As will be noted in this virtual issue, the development of enrichment methods has been a dynamic area of research. Enrichment is complicated by the sequence of the peptide, which can favor one type of method over another and by the number of phosphorylation sites within a peptide. These factors have led to efforts to improve methods and protocols for enrichment of phosphopeptides. As a result of the analytical developments over the past decade, powerful and robust workflows have been developed for large-scale phosphoproteomics and it is expected that development will continue. Compilation of this review taught us that many of the enabling methods used in phosphoproteomics are often disseminated in Journal of Proteome Research or Analytical Chemistry first, often a few years before they become the mainstream tools in more biology-oriented research applications. Through this issue we hope the most recent contributions will get extra attention to speed up their application to the mainstream of phosphoproteomics.
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Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands ∥ Netherlands Proteomics Centre, Utrecht, The Netherlands
AUTHOR INFORMATION
Notes
Views expressed in this editorial are those of the author and not necessarily the views of the ACS.
John R. Yates, III,† Associate Editor, Analytical Chemistry Shabaz Mohammed,‡ Senior Research Fellow Albert J. R. Heck,§,∥ Professor
† Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, United States ‡ Departments of Chemistry and Biochemistry, University of Oxford, Oxford, United Kingdom © 2014 American Chemical Society
Published: January 15, 2014 1313
dx.doi.org/10.1021/ac404019p | Anal. Chem. 2014, 86, 1313−1313
