Judging a protein by more than its name: GSK-3.
As knowledge of cellular signal transduction has accumulated, general truisms have emerged, including the notion that signaling proteins are usually activated by stimuli and that they, in turn, mediate the actions of specific agonists. Glycogen synthase kinase-3 (GSK-3) is an unusual protein-serine kinase that bucks these conventions. This evolutionarily conserved protein kinase is active in resting cells and is inhibited in response to activation of several distinct pathways, including those acting by elevation of 3' phosphorylated phosphatidylinositol lipids and adenosine 3'-5'-monophosphate (cAMP). In addition, GSK-3 is distinctly regulated by, and is a core component of, the Wnt pathway. This review describes the unique characteristics of this decidedly oddball protein kinase in terms of its diverse biological functions, plethora of targets, role in several human diseases, and consequential potential as a therapeutic target.
Woodgett
J R
JR
Ontario Cancer Institute within the Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario, M5G 2M9 Canada. jwoodget@oci.utoronto.ca
D000544:Alzheimer Disease / Q000188:drug therapy / Q000209:etiology; D000818:Animals; D001714:Bipolar Disorder / Q000188:drug therapy; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006801:Humans; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000502:physiology; D015398:Signal Transduction; D051153:Wnt Proteins; D029961:Zebrafish Proteins
D004791:Enzyme Inhibitors; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3