Protein Phosphatase 2A Is the Major Enzyme in Brain that Dephosphorylates τ Protein Phosphorylated by Proline-Directed Protein Kinases or Cyclic AMP-Dependent Protein Kinase |
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| Authors: | M Goedert R Jakes Z Qi J H Wang †P Cohen |
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| Institution: | MRC Laboratory of Molecular Biology, Cambridge, England;; Department of Biochemistry, University of Western Ontario, London, Ontario, Canada;and; MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dundee, Scotland |
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| Abstract: | Abstract: The paired helical filament (PHF), which makes up the major fibrous component of the neurofibrillary lesions of Alzheimer's disease, is composed of hyperphosphorylated and abnormally phosphorylated microtubule-associated protein τ. Previous studies have identified serine and threonine residues phosphorylated in PHF-τ and have shown that τ can be phosphorylated at several of these sites by proline-directed protein kinases and cyclic AMP-dependent protein kinase. Here we have investigated which protein phosphatase activities can dephosphorylate recombinant τ phosphorylated with mitogen-activated protein kinase, glycogen synthase kinase-3β, neuronal cdc2-like kinase, or cyclic AMP-dependent protein kinase. We show that protein phosphatase 2A is by far the major protein phosphatase activity in brain that dephosphorylates τ phosphorylated in this manner. |
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| Keywords: | Paired helical filaments τ protein Protein phosphatase 2A Dephosphorylation |
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