Protein kinases and their therapeutic exploitation.
This review focuses on the recognition properties of protein kinases at the molecular level. Phosphorylation of the substrate protein by a protein kinase can result in enzyme activation or inhibition, conformational changes that change recognition properties, or the creation of a surface with distinct binding properties. Protein kinases have become important targets for the development of inhibitors with potential therapeutic application. Various examples are considered in this review, and I discuss our own work on glycogen phosphorylase and phosphorylase kinase, and the structures of proteins involved with the cell cycle, including cyclins and cyclin-dependent kinases.
Johnson
L
L
Laboratory of Molecular Biophysics, University of Oxford, UK. louise.johnson@biop.ox.ac.uk
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002453:Cell Cycle; D003920:Diabetes Mellitus / Q000188:drug therapy; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D024981:Glycogen Phosphorylase / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy; D010764:Phosphorylase Kinase / Q000378:metabolism; D010766:Phosphorylation; D011487:Protein Conformation; D011494:Protein Kinases / Q000378:metabolism / Q000502:physiology*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D024981:Glycogen Phosphorylase; D011494:Protein Kinases; D010764:Phosphorylase Kinase