Glycogen synthase kinase-3 beta phosphorylates tau protein at multiple sites in intact cells.
Hyperphosphorylated tau protein is the major constituent of the paired helical filament (PHF), the major fibrous component of the neurofibrillary lesions of Alzheimer's disease (AD). Hyperphosphorylation of tau is believed to be the critical event that leads to filament assembly. Identification of the responsible protein kinases is therefore a key step towards an understanding of the pathogenesis of AD. Mitogen-activated protein kinase, glycogen synthase kinase-3 (GSK3) and neuronal cdc2-like kinase have been shown to phosphorylate tau protein in vitro at a number of sites that are phosphorylated in PHFs. In this study, we report that transient transfection of human GSK3 beta into Chinese hamster ovary cells stably transfected with individual human tau isoforms leads to hyperphosphorylation of tau at all the sites investigated with phosphorylation-dependent anti-tau antibodies. Thus, GSK3 beta is a protein kinase that phosphorylates tau protein in intact cells.
Sperber
B R
BR
Institute of Neurological Sciences, University of Pennsylvania, Philadelphia 19104, USA.
Leight
S
S
Goedert
M
M
Lee
V M
VM
D000409:Alanine / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D019084:Fluorescent Antibody Technique, Indirect; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006801:Humans; D015151:Immunoblotting; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D012694:Serine / Q000737:chemistry; D014162:Transfection; D016875:tau Proteins / Q000378:metabolism*
D016875:tau Proteins; D012694:Serine; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D000409:Alanine