Discovery of PDK1, one of the missing links in insulin signal transduction. Colworth Medal Lecture.
Historically, two strategies have been used to dissect the insulin signal transduction pathway. One was to start at the insulin receptor and work down the signal transduction pathway from the plasma membrane. The other was to select a physiological action of insulin, namely the mechanism by which insulin stimulates glycogen synthesis, and then work backwards towards the receptor. The hope was that eventually the groups working down from the top of the insulin signalling pathway would meet up with those working upwards from the bottom of the pathway. This has now happened, and in this lecture I will describe the recent advances that have linked the research from both ends of the insulin signal transduction pathway. I will also discuss how these findings have enabled pharmaceutical companies to embark on novel programmes to develop improved therapies for the treatment of diabetes in the future.
Alessi
D R
DR
MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K. d.r.alessi@dundee.ac.uk
D064413:3-Phosphoinositide-Dependent Protein Kinases; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003920:Diabetes Mellitus / Q000201:enzymology / Q000378:metabolism*; D004789:Enzyme Activation; D038362:Glycogen Synthase Kinase 3; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000187:drug effects
D007328:Insulin; D018129:Phosphatidylinositol Phosphates; D011518:Proto-Oncogene Proteins; C060974:phosphatidylinositol 3,4,5-triphosphate; D064413:3-Phosphoinositide-Dependent Protein Kinases; C578562:PDPK1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3