title: C-terminal truncation of GSK-3β enhances its dephosphorylation by PP2A.
abstract: Glycogen synthase kinase-3β (GSK-3β) is the major tau kinase. Its phosphorylation at Ser9 suppresses the activity. In Alzheimer's disease (AD) brain, GSK-3β is truncated at the C terminus by overactivated calpain I, leading to an increase in its activity. However, the effect of truncation on its phosphorylation is unknown. We found here that in AD brain and in cultured cells, C-terminally truncated GSK-3β is less phosphorylated at Ser9 than the full-length enzyme. The truncation promotes GSK-3β nuclear translocation and enhances its interaction with protein phosphatase 2A (PP2A), leading to dephosphorylation. Thus, the truncation of GSK-3β may enhance its activity through Ser9 dephosphorylation by PP2A. Our findings shed new light on the role of calpain-GSK-3β-PP2A in tau pathogenesis of AD.
authors.affiliation: Key laboratory of neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Regeneration, Nantong University, China.
authors.forename: Nana
authors.initials: N
authors.lastname: Jin
authors.affiliation: Key laboratory of neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Regeneration, Nantong University, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Key laboratory of neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Regeneration, Nantong University, China.|Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Xu
authors.affiliation: Key laboratory of neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Regeneration, Nantong University, China.|Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
authors.forename: Cheng-Xin
authors.initials: CX
authors.lastname: Gong
authors.affiliation: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
authors.forename: Khalid
authors.initials: K
authors.lastname: Iqbal
authors.affiliation: Key laboratory of neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Regeneration, Nantong University, China.|Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics; D000818:Animals; D001344:Autopsy / Q000379:methods; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D000071679:Glycogen Synthase Kinase 3 beta / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D009154:Mutation; D010766:Phosphorylation; D011180:Postmortem Changes; D011485:Protein Binding; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D013997:Time Factors
chemical_list: D012694:Serine; D000071679:Glycogen Synthase Kinase 3 beta; D054648:Protein Phosphatase 2
keywords: Alzheimer's disease; glycogen synthase kinase-3β; phosphorylation; protein phosphatase 2A; truncation