Protein Phosphorylation: A Major Switch Mechanism for Metabolic Regulation

Tremendous advances in MS-based phosphoproteomics have uncovered tens of thousands of phosphorylation sites on the majority of cellular proteins. Well-studied kinases and their substrates represent only a small fraction of the regulated phosphoproteome, suggesting that many important regulatory nodes remain unexplored. Metabolism is regulated by and regulates signal transduction in an intricate network of cellular and organismal regulation. Recent developments aimed at simplifying the phosphoproteomics workflow allow for many larger and in vivo studies, and promise to make the technology accessible to a wider audience. Metabolism research is undergoing a renaissance because many diseases are increasingly recognized as being characterized by perturbations in intracellular metabolic regulation. Metabolic changes can be conferred through changes to the expression of metabolic enzymes, the concentrations of substrates or products that govern reaction kinetics, or post-translational modification (PTM) of the proteins that facilitate these reactions. On the 60th anniversary since its discovery, reversible protein phosphorylation is widely appreciated as an essential PTM regulating metabolism. With the ability to quantitatively measure dynamic changes in protein phosphorylation on a global scale – hereafter referred to as phosphoproteomics – we are now entering a new era in metabolism research, with mass spectrometry (MS)-based proteomics at the helm. Metabolism research is undergoing a renaissance because many diseases are increasingly recognized as being characterized by perturbations in intracellular metabolic regulation. Metabolic changes can be conferred through changes to the expression of metabolic enzymes, the concentrations of substrates or products that govern reaction kinetics, or post-translational modification (PTM) of the proteins that facilitate these reactions. On the 60th anniversary since its discovery, reversible protein phosphorylation is widely appreciated as an essential PTM regulating metabolism. With the ability to quantitatively measure dynamic changes in protein phosphorylation on a global scale – hereafter referred to as phosphoproteomics – we are now entering a new era in metabolism research, with mass spectrometry (MS)-based proteomics at the helm.