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 Citations (Scopus)

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

Fingerprint

Neurofilament Proteins
Amino Acids
Peptides
Phosphorylation
Phosphoric Monoester Hydrolases
Antibodies
Brain
Alzheimer Disease
Molecular weight
Neurofibrillary Tangles
Neurites
Molecular Weight
Enzyme-Linked Immunosorbent Assay
Therapeutics
neurofilament protein H

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

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title = "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",
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.",
keywords = "Alzheimer's disease, Antibody, E9 peptide, Human τ, Paired helical filament, Phosphorylation",
author = "Liu, {Wan Kyng} and Dickson, {Dennis W} and Yen, {Shu Hui C}",
year = "1994",
month = "3",
language = "English (US)",
volume = "62",
pages = "1055--1061",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
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TY - JOUR

T1 - 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

AU - Liu, Wan Kyng

AU - Dickson, Dennis W

AU - Yen, Shu Hui C

PY - 1994/3

Y1 - 1994/3

N2 - 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.

AB - 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.

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KW - Antibody

KW - E9 peptide

KW - Human τ

KW - Paired helical filament

KW - Phosphorylation

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