The role of protein phosphorylation in human health and disease. The Sir Hans Krebs Medal Lecture.
The reversible phosphorylation of proteins regulates almost all aspects of cell life, while abnormal phosphorylation is a cause or consequence of many diseases. Mutations in particular protein kinases and phosphatases gives rise to a number of disorders and many naturally occurring toxins and pathogens exert their effects by altering the phosphorylation states of intracellular proteins. In this lecture, I present an overview of the progress that is being made in developing specific inhibitors of protein kinases for the treatment of cancer and chronic inflammatory diseases and describe how recent advances in our understanding of the specificity and regulation of one particular protein kinase (GSK3) may facilitate the development of drugs to treat diabetes that would not have the potential to be oncogenic. I also discuss the exploitation of specific protein kinase inhibitors for the study of cell signalling and make recommendations for their effective use in cell-based assays.
Cohen
P
P
MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 4HN, Scotland, UK. p.cohen@dundee.ac.uk
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D038362:Glycogen Synthase Kinase 3; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction; D020521:Stroke / Q000188:drug therapy
D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D011506:Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D010749:Phosphoprotein Phosphatases