ArticleThe Journal of biological chemistry2010
Spectroscopic studies of GSK3{beta} phosphorylation of the neuronal tau protein and its interaction with the N-terminal domain of apolipoprotein E.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 77 citations in OpenAlex.
- A coherent structural picture of the interaction of Tau with tubulin provides a link to its aggregation.The Journal of biological chemistry · 2026Review
- Accessing intractable, phosphorylated intrinsically disordered proteins via a protease-cleavable inclusion body tag.Protein science : a publication of the Protein Society · 2026Article
- Glycogen synthase kinase 3 (GSK3) inhibition: a potential therapeutic strategy for Alzheimer's disease.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Chronic Sustained Hypoxia Leads to Brainstem Tauopathy and Declines the Power of Rhythms in the Ventrolateral Medulla: Shedding Light on a Possible Mechanism.Molecular neurobiology · 2024Article
- Phosphorylation of Tau Protein by CDK2/cyclin A and GSK3β Recombinant Kinases: Analysis of Phosphorylation Patterns by Nuclear Magnetic Resonance Spectroscopy.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Tau, microtubule dynamics, and axonal transport: New paradigms for neurodegenerative disease.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Article
- Virtual Screening and Testing of GSK-3 Inhibitors Using Human SH-SY5Y Cells Expressing Tau Folding Reporter and Mouse Hippocampal Primary Culture under Tau Cytotoxicity.Biomolecules & therapeutics · 2023Article
- Apoe4 and Alzheimer's Disease Pathogenesis-Mitochondrial Deregulation and Targeted Therapeutic Strategies.International journal of molecular sciences · 2023Review
- Mammalian eIF4E2-GSK3β maintains basal phosphorylation of p53 to resist senescence under hypoxia.Cell death & disease · 2022Article
- Lithium modulates multiple tau kinases with distinct effects in cortical and hippocampal neurons according to concentration ranges.Naunyn-Schmiedeberg's archives of pharmacology · 2022Article
- Deciphering the Structure and Formation of Amyloids in Neurodegenerative Diseases With Chemical Biology Tools.Frontiers in chemistry · 2022Review
- Revisiting the Role of GSK3, A Modulator of Innate Immunity, in Idiopathic Inclusion Body Myositis.Cells · 2021Review
- Unambiguous Tracking of Protein Phosphorylation by Fast High-Resolution FOSY NMR*.Angewandte Chemie (International ed. in English) · 2021Article
- Diabetes and Alzheimer's Disease: Might Mitochondrial Dysfunction Help Deciphering the Common Path?Antioxidants (Basel, Switzerland) · 2021Review
- Programmed Cell Death Protein 1 Blockade Reduces Glycogen Synthase Kinase 3β Activity and Tau Hyperphosphorylation in Alzheimer's Disease Mouse Models.Frontiers in cell and developmental biology · 2021Article
- Phosphorylation andFrontiers in molecular neuroscience · 2021Article
- Glycogen synthase kinase (GSK)-3 and the double-strand RNA-dependent kinase, PKR: When two kinases for the common good turn bad.Biochimica et biophysica acta. Molecular cell research · 2020Review
- p63 uses a switch-like mechanism to set the threshold for induction of apoptosis.Nature chemical biology · 2020Article
- The role of APOE4 in Alzheimer's disease: strategies for future therapeutic interventions.Neuronal signaling · 2019Review
- In-Cell NMR Study of Tau and MARK2 Phosphorylated Tau.International journal of molecular sciences · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer disease neurons are characterized by extraneuronal plaques formed by aggregated amyloid-β peptide and by intraneuronal tangles composed of fibrillar aggregates of the microtubule-associated Tau protein. Tau is mostly found in a hyperphosphorylated form in these tangles. Glycogen synthase kinase 3β (GSK3β) is a proline-directed kinase generally considered as one of the major players that (hyper)phosphorylates Tau. The kinase phosphorylates mainly (Ser/Thr)-Pro motifs and is believed to require a priming activity by another kinase. Here, we use an in vitro phosphorylation assay and NMR spectroscopy to characterize in a qualitative and quantitative manner the phosphorylation of Tau by GSK3β. We find that three residues can be phosphorylated (Ser-396, Ser-400, and Ser-404) by GSK3β alone, without priming. Ser-404 is essential in this process, as its mutation to Ala prevents all activity of GSK3β. However, priming enhances the catalytic efficacy of the kinase, as initial phosphorylation of Ser-214 by the cAMP-dependent protein kinase (PKA) leads to the rapid modification by GSK3β of four regularly spaced additional sites. Because the regular incorporation of negative charges by GSK3β leads to a potential parallel between phospho-Tau and heparin, we investigated its interaction with the heparin/low density lipoprotein receptor binding domain of human apolipoprotein E. We indeed observed an interaction between the GSK3β-promoted regular phospho-pattern on Tau and the apolipoprotein E fragment but none in the absence of phosphorylation or the presence of an irregular phosphorylation pattern by the prolonged activity of PKA. Apolipoprotein E is therefore able to discriminate and interact with specific phosphorylation patterns of Tau.
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