Amino acid residues 226-240 of τ, which encompass the first Lys-Ser-Pro site of τ, are partially phosphorylated in Alzheimer paired helical filament-τ

Wan Kyng Liu, Dennis W Dickson, Shu Hui C Yen

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

A synthetic peptide corresponding to residues 226-240 (E9 peptide) of human τ, which contains an Lys-Ser-Pro motif, was used to raise a polyclonal antibody. The antibody, E9, was 10-fold less reactive with phospho-E9 peptide than with native E9 peptide. E9 antibody was used to study the extent of phosphorylation in a modified form of τ (PHF-τ) that is found in Alzheimer's disease brain and is incorporated into paired helical filaments (PHFs). E9 immunolabeled Alzheimer's disease neurofibrillary tangles and abnormal neurites in brain sections intensely, with increased immunoreactivity detected after pretreatment of sections with phosphatase. On immunoblots and ELISA, E9 reacted with PHF-τ and recombinant human τ but not with the high and middle molecular weight neurofilament proteins. Phosphatase treatment of PHF-τ improved the E9 immunoreactivity by 30-50%. Dephosphorylated high but not middle molecular weight neurofilament protein became reactive with E9. These results indicate that <50% of the PHF-τ is phosphorylated in the subregion corresponding to residues 226-240 of τ and suggest that the phosphorylation of this region may not be essential for PHF formation.

Original languageEnglish (US)
Pages (from-to)1055-1061
Number of pages7
JournalJournal of Neurochemistry
Volume62
Issue number3
StatePublished - Mar 1994
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Antibody
  • E9 peptide
  • Human τ
  • Paired helical filament
  • Phosphorylation

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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