title: Technologies and challenges in large-scale phosphoproteomics.
abstract: Phosphorylation, the reversible addition of a phosphate group to amino acid side chains of proteins, is a fundamental regulator of protein activity, stability, and molecular interactions. Most cellular processes, such as inter- and intracellular signaling, protein synthesis, degradation, and apoptosis, rely on phosphorylation. This PTM is thus involved in many diseases, rendering localization and assessment of extent of phosphorylation of major scientific interest. MS-based phosphoproteomics, which aims at describing all phosphorylation sites in a specific type of cell, tissue, or organism, has become the main technique for discovery and characterization of phosphoproteins in a nonhypothesis driven fashion. In this review, we describe methods for state-of-the-art MS-based analysis of protein phosphorylation as well as the strategies employed in large-scale phosphoproteomic experiments with focus on the various challenges and limitations this field currently faces.
authors: Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
authors: Kasper
authors: K
authors: Engholm-Keller
authors: Martin R
authors: MR
authors: Larsen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002846:Chromatography, Affinity; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000302:isolation & purification; D010750:Phosphoproteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction
chemical_list: D010446:Peptide Fragments; D010750:Phosphoproteins; D020543:Proteome