Overexpression of the mouse dishevelled-1 protein inhibits GSK-3beta-mediated phosphorylation of tau in transfected mammalian cells.
Tau is a neuronal microtubule-associated protein whose function is modulated by phosphorylation. GSK-3beta is a tau kinase. GSK-3beta is part of the wingless signalling pathway and stimulation by wingless is predicted to down-regulate GSK-3beta activity. In Drosophila imaginal disc cells, overexpression of dishevelled, a component of the wingless pathway, mimics the wingless signal. We have therefore studied the effect that overexpression of the murine dishevelled-1 protein has on GSK-3beta-mediated phosphorylation of tau in transfected CHO cells. We find that co-transfection with dishevelled-1 is inhibitory to GSK-3beta-mediated tau phosphorylation. Tau is hyperphosphorylated in Alzheimer's disease and the possible relevance of these findings to Alzheimer's disease pathogenesis are discussed.
Wagner
U
U
Department of Neuroscience, The Institute of Psychiatry, London, UK.
Brownlees
J
J
Irving
N G
NG
Lucas
F R
FR
Salinas
P C
PC
Miller
C C
CC
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D003001:Cloning, Molecular; D006224:Cricetinae; D000072261:Dishevelled Proteins; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3; D006801:Humans; D019476:Insect Proteins / Q000378:metabolism*; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics*; D010766:Phosphorylation; D015398:Signal Transduction; D014162:Transfection; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C000606578:DVL1 protein, human; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; C000606579:Dvl1 protein, mouse; D019476:Insect Proteins; D010750:Phosphoproteins; C000606588:dsh protein, Drosophila; D016875:tau Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3