Protein phosphatase 2A is the major enzyme in brain that dephosphorylates tau protein phosphorylated by proline-directed protein kinases or cyclic AMP-dependent protein kinase

J Neurochem. 1995 Dec;65(6):2804-7. doi: 10.1046/j.1471-4159.1995.65062804.x.


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 tau. Previous studies have identified serine and threonine residues phosphorylated in PHF-tau and have shown that tau 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 tau phosphorylated with mitogen-activated protein kinase, glycogen synthase kinase-3 beta, 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 tau phosphorylated in this manner.

MeSH terms

  • Brain / enzymology*
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Humans
  • Phosphoprotein Phosphatases / metabolism*
  • Phosphorylation
  • Proline-Directed Protein Kinases
  • Protein Phosphatase 2
  • Protein Serine-Threonine Kinases / metabolism*
  • Recombinant Proteins
  • tau Proteins / metabolism*


  • Recombinant Proteins
  • tau Proteins
  • Proline-Directed Protein Kinases
  • Protein Serine-Threonine Kinases
  • Cyclic AMP-Dependent Protein Kinases
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2