Detection of Phosphorylated Ser262 in Fetal Tau, Adult Tau, and Paired Helical Filament Tau
Open accessAbstract
Paired helical filaments (PHFs) are the major structural elements of Alzheimer's disease neurofibrillary lesions, and these filaments are formed from hyperphosphorylated brain tau known as PHF-tau. Recent studies showed that many previously identified phosphorylated residues in PHF-tau also are phosphate acceptor sites in fetal and rapidly processed adult brain tau. However, Ser262 has been suggested to be uniquely phosphorylated in PHF-tau and a key regulator of the binding of tau to microtubules. For these reasons, we generated a monoclonal antibody (12E8) specific for phosphorylated Ser262 and showed that 12E8 binds to PHF-tau, rat and human fetal brain tau, as well as to rapidly processed adult rat and biopsy-derived human brain tau. Further, phosphorylation Ser262 was developmentally regulated, and endogenous brain phosphatases rapidly dephosphorylated Ser262 in biopsy-derived brain tau isolates. Finally, the phosphorylation of Ser262 did not eliminate the binding of tau to microtubules. Thus, we speculate that the binding of tau to microtubules is regulated by phosphorylation at multiple sites and that the generation of PHF-tau in Alzheimer's disease results from the reduced efficiency of phosphatases leading to the incremental accumulation of hyperphosphorylated tau.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
No significant differences in phospho-tau levels relative to controls were observed for 12E8 and AT270 with modifiers from the EY screen.
“No significant differences in phospho-tau levels relative to controls were observed (Supplementary Material, Fig. S4).”
From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [85]
The immunoblot-analysis and 12E8 results passages describe tau phosphorylation and the 12E8 antibody, but do not report an EY modifier screen or a comparison with its controls. Searches for EY-screen modifiers and AT270 found no passage addressing the claimed absence of significant differences. Page numbers were not available in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 46 · Cited by 345
Research works printed but not linked: 4
- Goedert, M., Wischik, C. M.•Crowther. R. A., Walk er . J. E.•and Klug, A. (1988) Proc. No ll . Aead. Sci. U. S . A. 85, 4051 -4055
- Wischik, C. M., Novak , M., Thogersen, H. C., Edwa rds , P. C., Runswick, M. J ., J ak es, R., Walke r, J . E., Milste in, Coo Roth , M., a nd Klug, A. ()988) Proc. Natl. Acad. S ci. U. S. A. 85 , 4506-45 10
- Weingarten, M. D., Lockwood, A. a., Hwo, S.-Y., an d Kirschner, M. W. (1975 ) Proc. Na tl. Acad. S ci. U. S . A. 72 , 1858-1 863
- Goedert, M., Jakes, R., Crowt her , R. A., Six, J ., Lubke , U., Vandermeeren , M., Cras, P., Tr ojanow ski. J. Q., and Lee, V. M.-Y. (1993) Proc. N oll. A cad . Sci.
- Authors
- Seubert, P., Mawal-Dewan, M., Barbour, R., Jakes, R., Goedert, M., Johnson, G. V. W., Litersky, J. M., Schenk, D., Lieberburg, I., Trojanowski, J. Q., & Lee, V. M.-Y.
- Affiliations
- University of Pennsylvania (US)
- MRC Laboratory of Molecular Biology (GB)
- University of Alabama at Birmingham (US)
- Corresponding author
- Lee, Virginia M.-Y.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1995-08
- Volume
- 270
- Issue
- 32
- Pages
- 18917-18922
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2108177092
- Cited by
- 345
- References
- 46
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 3 · 2021: 6 · 2020: 5 · 2019: 4 · 2018: 6 · 2017: 5 · 2016: 8 · 2015: 8 · 2014: 6 · 2013: 8 · 2012: 13
- FWCI
- 11.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Public Health Foundation of India
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- tau protein, paired helical filaments, PHF-tau, Alzheimer's disease, neurofibrillary tangles, microtubule binding, phosphatase, hyperphosphorylated tau
- MeSH terms
- Adult, Alzheimer Disease, Amino Acid Sequence, Animals, Biopsy, Female, Fetus, Humans, Microtubules, Molecular Sequence Data, Phosphorylation, Pregnancy, Serine, tau Proteins, Rats, Sprague-Dawley, Mice, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
