title: Mass spectrometric tools for systematic analysis of protein phosphorylation.
abstract: The study of protein phosphorylation has long been performed one protein and one modification site at a time, with a major emphasis placed on the functional relevance of one or a small number of given phosphorylation event(s). This has enabled exquisitely detailed views of many intracellular signaling pathways but has left a large portion of the phosphoproteome relatively uncharted. The past several years have seen an explosion in the development of generic and global approaches to study protein phosphorylation, thanks in large part to advances in robotics, mass spectrometry, and computational biology. As of July 2011, there were more than 60,000 nonredundant phosphorylation sites for human proteins annotated in a large repository. This explosion of data has, however, highlighted important issues regarding both the reliability of these types of identifications and the problem of assigning function to each of these phosphorylation events. Parallel advances in the identification of consensus sites for kinases, and systematic mapping of protein-protein interactions in signaling pathways, have provided complementary information that should help in obtaining a more holistic view of signaling. Here, we provide a perspective on system-wide approaches based on mass spectrometry to understand phosphoregulation.
authors.affiliation: Samuel Lunenfeld Research Institute at Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Nicole
authors.initials: N
authors.lastname: St-Denis
authors.forename: Anne-Claude
authors.initials: AC
authors.lastname: Gingras
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods; D030562:Databases, Protein; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D013058:Mass Spectrometry; D010449:Peptide Mapping; D010455:Peptides / Q000032:analysis; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010750:Phosphoproteins / Q000032:analysis*; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D011494:Protein Kinases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction
chemical_list: D010455:Peptides; D010750:Phosphoproteins; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases