In vivo phosphorylation sites in fetal and adult rat tau
Open accessAbstract
Fetal tau and tau in paired helical filaments show similar immunoreactivities with several phosphorylation-dependent paired helical filament-polyclonals and monoclonals, suggesting that the two molecules share several distinct phosphorylated epitopes. To make clear the similarities and differences between the two, we have undertaken work to identify the in vivo phosphorylation sites in fetal rat tau. We have approached this problem by identifying phosphopeptides by means of mass spectrometry and sequencing of those phosphopeptides after modification with ethanethiol. Although remarkable heterogeneity was present, fetal tau was found to bear at most 10 phosphates at Ser-189, Ser-190, Ser-193, Ser-226, Ser-387, Ser-395, Thr-172, Thr-222, and, presumably, Ser-391 and Thr-208 (numbering is according to the longest form of rat tau; Kosik, K. S., Orecchio, L. D., Bakalis, S., and Neve, R. L. (1989) Neuron 2, 1389-1397). In contrast, adult rat tau was much less phosphorylated; only Thr-172, Ser-190, Ser-193, Thr-222, and Ser-395 were phosphorylated to a slight-to-moderate extent. All these sites except for Ser-189 and Ser-391 were followed by Pro residues. Thus, tau is an in vivo substrate for proline-directed protein kinase(s), and its phosphorylation state is developmentally regulated.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Hyperphosphorylation of Tau is linked to neurodegeneration, with phosphorylation of more than 20 sites shown in degenerated brains of Alzheimer's patients.
“However, hyperphosphorylation is linked to neurodegeneration with phosphorylation of more than 20 sites shown in the degenerated brains of Alzheimer's patients (Watanabe et al., 1993;Morishima-Kawashima et al., 1995;Stoothoff and Johnson, 2005).”
From Regulation of Mitochondrial Transport and Inter-Microtubule Spacing by Tau Phosphorylation at the Sites Hyperphosphorylated in Alzheimer's Disease (2012) · cites this paper as Watanabe et al., 1993
Cites
Protein sequence and mass spectrometric analyses of tau in the Alzheimer's disease brain
Hasegawa, M., Morishima-Kawashima, M., Takio, K., Suzuki, M., Titani, K., & Ihara, Y. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)41890-x · Cited by 430 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Lee, V. M.-Y., Goedert, M., & Trojanowski, J. Q. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1121 · Cited by 2,480 · see citing works
Arendt, T., Stieler, J. T., & Holzer, M. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.08.018 · Cited by 609 · see citing works
Tau phosphorylation in neuronal cell function and dysfunction
Johnson, G. V. W., & Stoothoff, W. H. (2004) · Journal of Cell Science · doi:10.1242/jcs.01558 · Cited by 624 · see citing works
Monoclonal antibody PHF‐1 recognizes tau protein phosphorylated at serine residues 396 and 404
Otvos, L., Feiner, L., Lang, E., Szendrei, G. I., Goedert, M., & Lee, V. M. (1994) · Journal of Neuroscience Research · doi:10.1002/jnr.490390607 · Cited by 488 · see citing works
Goedert, M., Jakes, R., Crowther, R. A., Cohen, P., Vanmechelen, E., Vandermeeren, M., & Cras, P. (1994) · Biochemical Journal · doi:10.1042/bj3010871 · Cited by 375 · see citing works
Shahpasand, K., Uemura, I., Saito, T., Asano, T., Hata, K., Shibata, K., Toyoshima, Y., Hasegawa, M., & Hisanaga, S.-I. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.5927-11.2012 · Cited by 206 · see citing works
Self-citationp53 is upregulated in Alzheimer's disease and induces tau phosphorylation in HEK293a cells
Hooper, C., Meimaridou, E., Tavassoli, M., Melino, G., Lovestone, S., & Killick, R. (2007) · Neuroscience Letters · doi:10.1016/j.neulet.2007.03.026 · Cited by 165 · see citing works
Kanai, Y., & Hirokawa, N. (1995) · Neuron · doi:10.1016/0896-6273(95)90298-8 · Cited by 144 · see citing works
Wada, Y., Ishiguro, K., Itoh, T. J., Uchida, T., Hotani, H., Saito, T., Kishimoto, T., & Hisanaga, S.-I. (1998) · Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a022174 · Cited by 58 · see citing works
Latimer, D. A., Gallo, J.-M., Lovestone, S., Miller, C. C. J., Hugh Reynolds, C., Marquardt, B., Stabel, S., Woodgett, J. R., & Anderton, B. H. (1995) · FEBS Letters · doi:10.1016/0014-5793(95)00434-b · Cited by 48 · see citing works
Nakata, R., Torii, T., Miyasaka, T., & Misonou, H. (2026) · Neuroscience Research · doi:10.1016/j.neures.2025.104987 · Cited by 3 · see citing works
- Authors
- Watanabe, A., Hasegawa, M., Suzuki, M., Takio, K., Morishima-Kawashima, M., Titani, K., Arai, T., Kosik, K. S., & Ihara, Y.
- Affiliations
- The University of Tokyo (JP)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1993-12
- Volume
- 268
- Issue
- 34
- Pages
- 25712-25717
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1530865401
- Cited by
- 231
- References
- 1
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 5 · 2018: 3 · 2017: 9 · 2016: 4 · 2015: 4 · 2014: 5 · 2013: 5 · 2012: 3
- FWCI
- 13.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- tau protein, phosphorylation sites, rat fetus, paired helical filaments, phosphopeptides, proline-directed protein kinases, developmental regulation, phosphorylation state, serine/threonine phosphorylation
- MeSH terms
- Aging, Amino Acid Sequence, Animals, Brain, Cyanogen Bromide, Fetus, Molecular Sequence Data, Peptide Fragments, Endopeptidases, Phosphopeptides, Phosphorylation, Proline, Mass Spectrometry, tau Proteins, 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
