title: 14-3-3zeta facilitates GSK3beta-catalyzed tau phosphorylation in HEK-293 cells by a mechanism that requires phosphorylation of GSK3beta on Ser9.
abstract: Hyperphosphorylated tau is the prominent component of paired helical filaments, which are the major component of neurofibrillary tangles associated with Alzheimer's disease (AD). Glycogen synthase kinase 3beta (GSK3beta) is implicated to phosphorylate tau in normal and AD brain. Previously, we isolated a large multiprotein complex containing tau, Ser9-phosphorylated GSK3beta and 14-3-3zeta from bovine brain microtubules. We showed that within the complex, 14-3-3zeta binds to tau and GSK3beta and mediates GSK3beta-catalyzed tau phosphorylation. A recent report however indicated that 14-3-3zeta does not bind to tau or GSK3beta and does not increase tau phosphorylation by GSK3beta in cell models [T.A. Matthews, G.V.W. Johnson, Neurosci. Lett. 384 (2005) 211-216]. In the current study we have thoroughly analyzed the binding of 14-3-3zeta with tau and GSK3beta and evaluated the effect of 14-3-3zeta on tau phosphorylation by GSK3beta in HEK-293 cells. We found that 14-3-3zeta binds to tau and Ser9-phosphorylated GSK3beta. Nonphosphorylated GSK3beta phosphorylates tau without being influenced by 14-3-3zeta. Ser9-phosphorylated GSK3beta on the other hand phosphorylates tau significantly only in the presence of 14-3-3zeta. Our data demonstrate that 14-3-3zeta mediates tau phosphorylation by Ser9-phosphorylated GSK3beta in HEK-293 cells.
authors.affiliation: Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, 3755 Cote Ste Catherine, and Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec H3T 1E2, Canada.
authors.forename: Tong
authors.initials: T
authors.lastname: Li
authors.forename: Hemant K
authors.initials: HK
authors.lastname: Paudel
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology; D020134:Catalytic Domain / Q000502:physiology; D002460:Cell Line; D004789:Enzyme Activation / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology; D012694:Serine / Q000378:metabolism*; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D016875:tau Proteins; D012694:Serine; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3