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Neurochemical Research

, Volume 30, Issue 2, pp 277–287 | Cite as

Phosphothreonine-212 of Alzheimer Abnormally Hyperphosphorylated Tau is a Preferred Substrate of Protein Phosphatase-1

  • Abdur Rahman
  • Inge Grundke-Iqbal
  • Khalid Iqbal
Article

Abstract

We isolated and characterized several phosphoseryl/phosphothreonyl phosphatase activities (P1–P11) from frontal lobe of six autopsied human brains. Of these, PP1 (P3) was a major tau phosphatase. The enzyme required metal ions and was maximally activated by Mn2+. Western blots with antibodies to known protein phosphatases showed PP1 and PP2B immunoreactivity. However, the removal of PP2B by immunoabsorption or its inhibition with EGTA did not result in appreciable loss of P3 activity. These observations suggest that P3 was an enriched PP1. Dephosphorylation of Alzheimer disease hyperphosphorylated tau (AD P-tau) by PP1 was site-specific. PP1 preferentially dephosphorylated pT212 (40%), pT217 (26%), pS262 (33%), pS396 (42%) and pS422 (31%) of AD P-tau. Dephosphorylation of tau at pT181, pS199, pS202, pT205, pS214, and pS404, was undetectable. Of the sites dephosphorylated, pT212 was only a substrate for PP1, as purified/enriched PP2A and PP2B from the same brains did not dephosphorylate this site.

Keywords

protein phosphatase1 hyperphosphorylated tau site-specific dephosphorylation Alzheimer disease phosphothreonine-212 

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Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Abdur Rahman
    • 1
  • Inge Grundke-Iqbal
    • 1
  • Khalid Iqbal
    • 1
  1. 1.Department of NeurochemistryNew York Institute for Basic Research in Developmental DisabilitiesStaten IslandUSA

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