title: Alzheimer's disease abnormally phosphorylated tau is dephosphorylated by protein phosphatase-2B (calcineurin).
abstract: Abnormally hyperphosphorylated tau is the major protein subunit of paired helical filaments in Alzheimer brains. We have examined its site-specific dephosphorylation by different protein phosphatases. Dephosphorylation of tau was monitored by its interaction with several phosphorylation-dependent antibodies. Alzheimer tau was dephosphorylated by brain protein phosphatase-2B at the abnormally phosphorylated sites Ser46, Ser199, Ser202, Ser235, Ser396, and Ser404, and its relative mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis shifted to that of normal tau. Protein phosphatases-1 and -2A could dephosphorylate only some of the above six phosphorylation sites. These results indicate that protein phosphatase-2B might be involved in hyperphosphorylation of tau in Alzheimer's disease.
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314.
authors.forename: C X
authors.initials: CX
authors.lastname: Gong
authors.forename: T J
authors.initials: TJ
authors.lastname: Singh
authors.forename: I
authors.initials: I
authors.lastname: Grundke-Iqbal
authors.forename: K
authors.initials: K
authors.lastname: Iqbal
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D019703:Calcineurin; D002147:Calmodulin / Q000494:pharmacology; D002148:Calmodulin-Binding Proteins / Q000494:pharmacology*; D002413:Cations, Divalent / Q000494:pharmacology; D006801:Humans; D010749:Phosphoprotein Phosphatases / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D013997:Time Factors; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D002413:Cations, Divalent; D016875:tau Proteins; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases