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Protein sequence and mass spectrometric analyses of tau in the Alzheimer's disease brain
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Tau with unusually slow mobilities in sodium dodecyl sulfate-polyacrylamide gel electrophoresis was purified from the Sarkosyl-insoluble pellet of Alzheimer's disease brain homogenates. Such species of tau (PHF-tau) are considered to construct the framework of the sodium dodecyl sulfate-soluble form of paired helical filaments (PHF). Detailed comparison of peptide maps of PHF-tau and normal tau before and after dephosphorylation pointed to three anomalously eluted peaks which contained abnormally phosphorylated peptides, residues 191-225, 226-240, 260-267, and 386-438, according to the numbering of the longest tau isoform (Goedert, M., Spillantini, M. G., Jakes, R., Rutherford, D., and Crowther, R. A. (1989) Neuron 3, 519-526). Protein sequence and mass spectrometric analyses localized Thr-231 and Ser-235 as the abnormal phosphorylation sites and further indicated that each tau 1 site (residues 191-225) and the most carboxyl-terminal portion of the protein (residues 386-438) carries more than two abnormal phosphates. Ser-262 was also phosphorylated in a fraction of PHF-tau. Modifications other than phosphorylation, removal of the initiator methionine, and N alpha-acetylation at the amino terminus and deamidation at 2 asparaginyl residues were found in PHF-tau, but these modifications were also present in normal tau.
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“Prior studies have shown that many phosphorylated residues in PHF-tau are serines or threonines followed by a proline [1,6,8,11].”
From Glycogen synthase kinase-3β phosphorylates tau protein at multiple sites in intact cells (1995) · cites this paper as [8]
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Tau Protein and Alzheimer Paired Helical Filament Assembly: Interacting Domains and Control Residues
Mandelkow, E., Schweers, O., Biernat, J., Trinczek, B., Drewes, G., & Mandelkow�, E. (1996) · Springer eBooks · doi:10.1007/978-3-642-80109-9_10
Metadata
- Authors
- Hasegawa, M., Morishima-Kawashima, M., Takio, K., Suzuki, M., Titani, K., & Ihara, Y.
- Affiliations
- The University of Tokyo (JP)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1992-10
- Volume
- 267
- Issue
- 24
- Pages
- 17047-17054
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1598318710
- Cited by
- 430
- References
- 43
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 8 · 2023: 10 · 2022: 7 · 2021: 8 · 2020: 19 · 2019: 14 · 2018: 10 · 2017: 3 · 2016: 17 · 2015: 11 · 2014: 5 · 2013: 10 · 2012: 9
- FWCI
- 22.71
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- tau protein, Alzheimer's disease, paired helical filaments, phosphorylation sites, dephosphorylation, peptide mapping, protein modification, N-terminal acetylation, deamidation
- MeSH terms
- Alzheimer Disease, Amino Acid Sequence, Brain, Brain Chemistry, Electrophoresis, Polyacrylamide Gel, Humans, Molecular Sequence Data, Peptide Fragments, Peptide Mapping, Mass Spectrometry, tau Proteins
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