title: Regulation of the phosphorylation state and microtubule-binding activity of Tau by protein phosphatase 2A.
abstract: Recently, we reported that a pool of protein phosphatase 2A (PP2A) is associated with microtubules. Here, we demonstrate that specific isoforms of PP2A bind and dephosphorylate the neuronal microtubule-associated protein tau. Coexpression of tau and SV40 small t, a specific inhibitor of PP2A, in CV-1, NIH 3T3, or NT2 cells induced the phosphorylation of tau at multiple sites, including Ser-199, Ser-202, Thr-205, Ser-396, and Ser-404. Immunofluorescent and biochemical analyses revealed that hyperphosphorylation correlated with dissociation of tau from microtubules and a loss of tau-induced microtubule stabilization. Taken together, these results support the hypothesis that PP2A controls the phosphorylation state of tau in vivo.
authors.affiliation: Department of Pharmacology, University of Texas, Southwestern Medical Center, Dallas 75235, USA.
authors.forename: E
authors.initials: E
authors.lastname: Sontag
authors.forename: V
authors.initials: V
authors.lastname: Nunbhakdi-Craig
authors.forename: G
authors.initials: G
authors.lastname: Lee
authors.forename: G S
authors.initials: GS
authors.lastname: Bloom
authors.forename: M C
authors.initials: MC
authors.lastname: Mumby
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D004355:Drug Stability; D000939:Epitopes; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D054648:Protein Phosphatase 2; D016875:tau Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
chemical_list: D000939:Epitopes; D007527:Isoenzymes; D016875:tau Proteins; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2