ArticleThe Biochemical journal2001
The kinase DYRK phosphorylates protein-synthesis initiation factor eIF2Bepsilon at Ser539 and the microtubule-associated protein tau at Thr212: potential role for DYRK as a glycogen synthase kinase 3-priming kinase.
Article in The Biochemical journal, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers.
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147 citing papers in PubMed, 329 citations in OpenAlex.
- Overexpression of DYRK1A in down syndrome: Analysis of kinase activity.Biochemistry and biophysics reports · 2026Article
- Elevated DYRK1A in Primary Tauopathies and Therapeutic Targeting with the Brain-Penetrant Inhibitor DYR533.Research square · 2026Article
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Mapping the Brain Interaction Network of the Dual-Specificity, Tyrosine Phosphorylation-Regulated Kinase 1A (DYRK1A) Targeted by Leucettinib-21 Using Affinity Chromatography.ACS pharmacology & translational science · 2026Article
- Nitrogen-Doped Graphene Quantum Dots Conjugated to Leucettinib-21 Rescue Differentiating Zebrafish Purkinje Cells by Inhibiting Dyrk1A Kinase.ACS applied nano materials · 2026Article
- The dual fate of DYRK2 in cancer: balancing the light and dark side of tumorigenesis.Cancer metastasis reviews · 2026Review
- Increased Protein Synthesis With Reduced Endoplasmic Reticulum Stress Defines a Specific Adaptation in Pancreatic Acinar Metaplasia.Gastro hep advances · 2026Article
- Plasma p-tau212 identifies cognitively unimpaired individuals with emerging amyloid-β pathology.Journal of neurology · 2025Article
- Pathological Calcium Signaling in Traumatic Brain Injury and Alzheimer's Disease: From Acute Neuronal Injury to Chronic Neurodegeneration.International journal of molecular sciences · 2025Review
- Review
- Proinflammatory transcriptomic and kinomic alterations in astrocytes derived from patients with familial Alzheimer's disease.Brain, behavior, & immunity - health · 2025Article
- Unlocking the Therapeutic Potential of the Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A Inhibitors in Alzheimer's Diseases.Molecular neurobiology · 2025Review
- Lithium normalizes ASD-related neuronal, synaptic, and behavioral phenotypes in DYRK1A-knockin mice.Molecular psychiatry · 2025Article
- Plasma p-tau212 as a biomarker of sporadic and Down syndrome Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Calcineurin inhibition may prevent Alzheimer disease in people with Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Spatial differences in gene expression across the dorsal raphe nucleus in a model of early Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2025Article
- Updates in Alzheimer's disease: from basic research to diagnosis and therapies.Translational neurodegeneration · 2024Review
- DYRK1A is a multifunctional host factor that regulates coronavirus replication in a kinase-independent manner.Journal of virology · 2024Article
- Re-Arranging the Puzzle between the Amyloid-Beta and Tau Pathology: An APP-Centric Approach.International journal of molecular sciences · 2023Review
- Identification of FAM53C as a cytosolic-anchoring inhibitory binding protein of the kinase DYRK1A.Life science alliance · 2023Article
87 more citing papers are in PubMed but not listed here.
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7 authors at 3 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
The substrate specificity of glycogen synthase kinase 3 (GSK3) is unusual in that efficient phosphorylation only occurs if another phosphoserine or phosphothreonine residue is already present four residues C-terminal to the site of GSK3 phosphorylation. One such substrate is the epsilon-subunit of rat eukaryotic protein-synthesis initiation factor 2B (eIF2Bepsilon), which is inhibited by the GSK3-catalysed phosphorylation of Ser(535). There is evidence that GSK3 is only able to phosphorylate eIF2Bepsilon at Ser(535) if Ser(539) is already phosphorylated by another protein kinase. However, no protein kinases capable of phosphorylating Ser(539) have so far been identified. Here we show that Ser(539) of eIF2Bepsilon, which is followed by proline, is phosphorylated specifically by two isoforms of dual-specificity tyrosine phosphorylated and regulated kinase (DYRK2 and DYRK1A), but only weakly or not at all by other 'proline-directed' protein kinases tested. We also establish that phosphorylation of Ser(539) permits GSK3 to phosphorylate Ser(535) in vitro and that eIF2Bepsilon is highly phosphorylated at Ser(539) in vivo. The DYRK isoforms also phosphorylate human microtubule-associated protein tau at Thr(212) in vitro, a residue that is phosphorylated in foetal tau and hyperphosphorylated in filamentous tau from Alzheimer's-disease brain. Phosphorylation of Thr(212) primes tau for phosphorylation by GSK3 at Ser(208) in vitro, suggesting a more general role for DYRK isoforms in priming phosphorylation of GSK3 substrates.
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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.