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Phosphorylation by cAMP-dependent protein kinase inhibits the degradation of tau by calpain.
Open accessAbstract
The effects of cAMP-dependent protein kinase (cAMP-PK) phosphorylation on the degradation of the microtubule-associated protein tau by calpain were studied. Purified bovine brain tau that had been phosphorylated by cAMP-PK had a slower migration pattern on sodium dodecyl sulfate-polyacrylamide gels and a more acidic, less heterogeneous pattern on two-dimensional, nonequilibrium pH gradient electrophoresis (NEPHGE) gels compared with untreated tau. Phosphorylation of tau by cAMP-PK significantly inhibited its proteolysis by calpain compared with untreated tau. To our knowledge this is the first demonstration that phosphorylation of tau by a specific kinase results in increased resistance to hydrolysis by calpain. Tau dephosphorylated by alkaline phosphatase migrated more rapidly on sodium dodecyl sulfate-polyacrylamide gels and also showed an altered two-dimensional NEPHGE pattern. Dephosphorylation of tau had no effect on its susceptibility to calpain proteolysis, indicating that regulation of the susceptibility to calpain hydrolysis is due to the phosphorylation of a specific site(s). These results suggest a role for phosphorylation in regulating the degradation of tau. Abnormal phosphorylation could result in a protease-resistant tau population which may contribute to the formation of paired helical filaments in Alzheimer's disease.
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“phosphorylation of tau by PKA inhibits calpain-mediated tau proteolysis”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [210]
In the citing paper
“and NFTs are resistant to calpain cleavage [210, 211].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [210]
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Metadata
- Authors
- Litersky, J. M., & Johnson, G. V.
- Affiliations
- University of Alabama (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1992-01
- Volume
- 267
- Issue
- 3
- Pages
- 1563-1568
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1531327859
- Cited by
- 201
- References
- 52
- Citations by year
- 2026: 1 · 2024: 4 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 2 · 2018: 2 · 2017: 3 · 2016: 1 · 2015: 3 · 2013: 4 · 2012: 6
- FWCI
- 8.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01ag006569-13)
- National Institute on Aging (AG06569)
- National Institute of Neurological Disorders and Stroke (NS-27538)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Calpain Protease Function and Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
- Keywords
- tau protein, protein kinase A, phosphorylation, calpain, proteolysis, microtubule-associated proteins, dephosphorylation, protease resistance, Alzheimer's disease, paired helical filaments
- MeSH terms
- Animals, Autoradiography, Brain, Calpain, Cattle, Electrophoresis, Polyacrylamide Gel, Kinetics, Microtubules, Phosphorus Radioisotopes, Phosphorylation, Protein Kinases, Immunoblotting, Electrophoresis, Gel, Two-Dimensional, tau Proteins
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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 ›
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