Cited by 201Alzheimer's disease research and treatmentsCalpain Protease Function and RegulationS100 Proteins and Annexins

Phosphorylation by cAMP-dependent protein kinase inhibits the degradation of tau by calpain.

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Litersky, J M, Johnson, G V·1992·Journal of Biological Chemistry

Abstract

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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Crossref · 10.1016/s0021-9258(18)45982-0

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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
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
  • Health Sciences › Medicine › Physiology › 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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