Microtubule-Stimulated Phosphorylation of tau at Ser202 and Thr205 by cdk5 Decreases Its Microtubule Nucleation Activity
Abstract
Phosphorylation of tau, a heat-stable neuron-specific microtubule-associated protein, by cdk5 was stimulated in the presence of microtubules (MTs). This stimulation was due to an increased phosphorylation rate and there was no increase in total amount of phosphorylation. Two-dimensional phosphopeptide map analysis showed that MTs stimulated phosphorylation of a specific peptide. Using Western blotting with antibodies that the recognized phosphorylation-dependent epitopes within tau, the phosphorylation sites stimulated by the presence of MTs were found to be Ser202 and Thr205 (numbered according to the human tau isoform containing 441 residues). MT-dependent phosphorylation at Thr205 was observed in situ in rat cerebrum primary cultured neurons. Stimulated phosphorylation at Ser202 and Thr205 decreased the MT-nucleation activity of tau, which is in contrast to MT-independent phosphorylation at Ser235 and Ser404.
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Tau phosphorylation at S202/T205 as detected by the AT8 antibody is commonly found in tauopathies.
“Tau phosphorylation at S202/T205 as detected by the AT8 antibody (80) is commonly found in tauopathies (38,81–84).”
From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [38]
Phosphorylation at major Ser-Pro/Thr-Pro sites reduces but does not abolish Tau binding to MTs, leading to more dynamic MTs.
“Phosphorylation at these sites reduces, but does not abolish, Tau binding to MTs, leading to more dynamic MTs (Wada et al., 1998;Liu et al., 2007).”
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 Wada et al., 1998
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- Authors
- Wada, Y., Ishiguro, K., Itoh, T. J., Uchida, T., Hotani, H., Saito, T., Kishimoto, T., & Hisanaga, S.-I.
- Affiliations
- Tokyo Institute of Technology (JP)
- Venue
- Journal of Biochemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 1998-10-01
- Volume
- 124
- Issue
- 4
- Pages
- 738-746
- ISSN
- 0021-924X (ISSN-L)
- OpenAlex
- W2040383902
- Cited by
- 58
- References
- 49
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 5 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 2 · 2014: 2 · 2013: 2 · 2012: 7
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- tau protein, cyclin-dependent kinase 5, microtubule nucleation, microtubule-associated proteins, tau phosphorylation sites, phosphopeptide mapping
- MeSH terms
- Animals, Epitopes, Brain, Cells, Cultured, Embryo, Mammalian, Humans, Kinetics, Microtubules, Neurons, Peptide Mapping, Phosphopeptides, Phosphorylation, Serine, Swine, Threonine, Blotting, Western, Nocodazole, tau Proteins, Protein Serine-Threonine Kinases, Cyclin-Dependent Kinases, Cyclin-Dependent Kinase 5, Rats
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