ArticleThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology2014
Regulatory B Subunits of Protein Phosphatase 2A Are Involved in Site-specific Regulation of Tau Protein Phosphorylation.
Article in The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 34 citations in OpenAlex.
- PP2A phosphatase regulates Hippo signalling in dual manner.The EMBO journal · 2026Article
- Ptprd deficiency promotes tau hyperphosphorylation and impairs cognitive function in aged mice.Biological research · 2025Article
- A de novo missense mutation in PPP2R5D alters dopamine pathways and morphology of iPSC-derived midbrain neurons.Stem cells (Dayton, Ohio) · 2025Article
- Protein Phosphatase 2A Regulates Phenotypic and Metabolic Alteration of Microglia Cells in HFD-Associated Vascular Dementia Mice via TNF-α/Arg-1 Axis.Molecular neurobiology · 2023Article
- Emerging evidence for dysregulated proteome cargoes of tau-propagating extracellular vesicles driven by familial mutations of tau and presenilin.Extracellular vesicles and circulating nucleic acids · 2023Article
- The role of serine/threonine phosphatases in human development: Evidence from congenital disorders.Frontiers in cell and developmental biology · 2022Review
- Mutant Presenilin 1 Dysregulates Exosomal Proteome Cargo Produced by Human-Induced Pluripotent Stem Cell Neurons.ACS omega · 2021Article
- Altered Cerebrospinal Fluid Exosomal microRNA Levels in Young-Onset Alzheimer's Disease and Frontotemporal Dementia.Journal of Alzheimer's disease reports · 2021Article
- Partial Inhibition of Mitochondrial Complex I Reduces Tau Pathology and Improves Energy Homeostasis and Synaptic Function in 3xTg-AD Mice.Journal of Alzheimer's disease : JAD · 2021Article
- Early-Onset Parkinsonism Is a Manifestation of the PPP2R5D p.E200K Mutation.Annals of neurology · 2020Article
- PPP2R5D-Related Intellectual Disability and Neurodevelopmental Delay: A Review of the Current Understanding of the Genetics and Biochemical Basis of the Disorder.International journal of molecular sciences · 2020Review
- Dysregulation of PP2A-Akt interaction contributes to Sucrose non-fermenting related kinase (SNRK) deficiency induced insulin resistance in adipose tissue.Molecular metabolism · 2019Article
- UBE3A-mediated PTPA ubiquitination and degradation regulate PP2A activity and dendritic spine morphology.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- To be or not to be: PP2A as a dual player in CNS functions, its role in neurodegeneration, and its interaction with brain insulin signaling.Cellular and molecular life sciences : CMLS · 2019Review
- Cancer driver mutations in endometriosis: Variations on the major theme of fibrogenesis.Reproductive medicine and biology · 2018Review
- Proteomic Analysis of the Peri-Infarct Area after Human Umbilical Cord Mesenchymal Stem Cell Transplantation in Experimental Stroke.Aging and disease · 2016Article
- Changes in microtubule-associated protein tau during peripheral nerve injury and regeneration.Neural regeneration research · 2016Article
- Amyloid Beta-Mediated Hypomethylation of Heme Oxygenase 1 Correlates with Cognitive Impairment in Alzheimer's Disease.PloS one · 2016Article
- De novo missense variants in PPP2R5D are associated with intellectual disability, macrocephaly, hypotonia, and autism.Neurogenetics · 2016Article
- Pathway Analysis Based on a Genome-Wide Association Study of Polycystic Ovary Syndrome.PloS one · 2015Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Overexpression of amyloid precursor protein with the Swedish mutation causes abnormal hyperphosphorylation of the microtubule-associated protein tau. Hyperphosphorylated isoforms of tau are major components of neurofibrillary tangles, which are histopathological hallmarks of Alzheimer's disease. Protein phosphatase 2A (PP2A), a major tau protein phosphatase, consists of a structural A subunit, catalytic C subunit, and a variety of regulatory B subunits. The B subunits have been reported to modulate function of the PP2A holoenzyme by regulating substrate binding, enzyme activity, and subcellular localization. In the current study, we characterized regulatory B subunit-specific regulation of tau protein phosphorylation. We showed that the PP2A B subunit PPP2R2A mediated dephosphorylation of tau protein at Ser-199, Ser-202/Thr-205, Thr-231, Ser-262, and Ser-422. Down-regulation of PPP2R5D expression decreased tau phosphorylation at Ser-202/Thr-205, Thr-231, and Ser-422, which indicates activation of the tau kinase glycogen synthase kinase 3 beta (GSK3β) by PP2A with PPP2R5D subunit. The level of activating phosphorylation of the GSK3β kinase Akt at Thr-308 and Ser-473 were both increased by PPP2R5D knockdown. We also characterized B subunit-specific phosphorylation sites in tau using mass spectrometric analysis. Liquid chromatography-mass spectrometry revealed that the phosphorylation status of the tau protein may be affected by PP2A, depending on the specific B subunits. These studies further our understanding of the function of various B subunits in mediating site-specific regulation of tau protein phosphorylation.
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