ArticleThe Journal of biological chemistry2013
Prostate-derived sterile 20-like kinases (PSKs/TAOKs) phosphorylate tau protein and are activated in tangle-bearing neurons in Alzheimer disease.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- The role of septin 7 in physiology and pathological disease: A systematic review of current status.Journal of cellular and molecular medicine · 2018Pooled it
- Structural and mechanistic characterization of heparin interactions with tau fibrils.The Journal of biological chemistry · 2026Article
- A Scalable Design for Proximity-Inducing Molecules.bioRxiv : the preprint server for biology · 2026Article
- Discovery of VU6083859, a TAOK1 Selective Inhibitor, and VU6080195, aACS chemical neuroscience · 2026Article
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- Elevated Levels of Extracellular Vesicle-Associated TAOK1 in Plasma: A Diagnostic Marker for Cognitive Decline in Parkinson's Disease Dementia and Alzheimer's Disease.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Biomarkers and Target-Specific Small-Molecule Drugs in Alzheimer's Diagnostic and Therapeutic Research: From Amyloidosis to Tauopathy.Neurochemical research · 2024Review
- Plasma p-tau212 antemortem diagnostic performance and prediction of autopsy verification of Alzheimer's disease neuropathology.Nature communications · 2024Article
- Characterization of mitochondria-associated ER membranes in the enteric nervous system under physiological and pathological conditions.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- p-tau Ser356 is associated with Alzheimer's disease pathology and is lowered in brain slice cultures using the NUAK inhibitor WZ4003.Acta neuropathologica · 2024Article
- Pleiotropic functions of TAO kinases and their dysregulation in neurological disorders.Science signaling · 2024Review
- Plasma p-tau212: antemortem diagnostic performance and prediction of autopsy verification of Alzheimer's disease neuropathology.medRxiv : the preprint server for health sciences · 2023Article
- Targeting autophagy in Alzheimer's disease: Animal models and mechanisms.Zoological research · 2023Review
- Article
- Targeted Dephosphorylation of Tau by Phosphorylation Targeting Chimeras (PhosTACs) as a Therapeutic Modality.Journal of the American Chemical Society · 2023Article
- Insights fromFrontiers in neuroscience · 2023Review
- A machine learning approach to brain epigenetic analysis reveals kinases associated with Alzheimer's disease.Nature communications · 2021Article
- Alzheimer's Disease Animal Models: Elucidation of Biomarkers and Therapeutic Approaches for Cognitive Impairment.International journal of molecular sciences · 2021Review
- Hippo signaling: bridging the gap between cancer and neurodegenerative disorders.Neural regeneration research · 2021Article
- Kinase Signaling in Dendritic Development and Disease.Frontiers in cellular neuroscience · 2021Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
In Alzheimer disease (AD), the microtubule-associated protein tau is highly phosphorylated and aggregates into characteristic neurofibrillary tangles. Prostate-derived sterile 20-like kinases (PSKs/TAOKs) 1 and 2, members of the sterile 20 family of kinases, have been shown to regulate microtubule stability and organization. Here we show that tau is a good substrate for PSK1 and PSK2 phosphorylation with mass spectrometric analysis of phosphorylated tau revealing more than 40 tau residues as targets of these kinases. Notably, phosphorylated residues include motifs located within the microtubule-binding repeat domain on tau (Ser-262, Ser-324, and Ser-356), sites that are known to regulate tau-microtubule interactions. PSK catalytic activity is enhanced in the entorhinal cortex and hippocampus, areas of the brain that are most susceptible to Alzheimer pathology, in comparison with the cerebellum, which is relatively spared. Activated PSK is associated with neurofibrillary tangles, dystrophic neurites surrounding neuritic plaques, neuropil threads, and granulovacuolar degeneration bodies in AD brain. By contrast, activated PSKs and phosphorylated tau are rarely detectible in immunostained control human brain. Our results demonstrate that tau is a substrate for PSK and suggest that this family of kinases could contribute to the development of AD pathology and dementia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.