title: Dephosphorylation of microtubule-associated protein tau by protein phosphatase-1 and -2C and its implication in Alzheimer disease.
abstract: Microtubule-associated protein tau is abnormally hyperphosphorylated and forms the major protein subunit of paired helical filaments (PHF) in Alzheimer disease brains. The abnormally phosphorylated sites Ser-199, Ser-202, Ser-396 and Ser-404 but not Ser-46 and Ser-235 of Alzheimer tau were found to be dephosphorylated by protein phosphatase-1 and this dephosphorylation was activated by Mn2+. In contrast, protein phosphatase-2C did not dephosphorylate any of these sites. Both protein phosphatase-1 and -2C had high activities towards [32P]tau phosphorylated by cAMP-dependent protein kinase. These results suggest that both protein phosphatase-1 and -2C might be associated with normal phosphorylation state of tau, but only the former and not the latter phosphatase is involved in its abnormal phosphorylation in Alzheimer disease.
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314.
authors.forename: C X
authors.initials: CX
authors.lastname: Gong
authors.forename: I
authors.initials: I
authors.lastname: Grundke-Iqbal
authors.forename: Z
authors.initials: Z
authors.lastname: Damuni
authors.forename: K
authors.initials: K
authors.lastname: Iqbal
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D054645:Protein Phosphatase 1; D011817:Rabbits; D012694:Serine / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D012694:Serine; D017868:Cyclic AMP-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1