ArticleMolecular biology of the cell1999
The development of cell processes induced by tau protein requires phosphorylation of serine 262 and 356 in the repeat domain and is inhibited by phosphorylation in the proline-rich domains.
Article in Molecular biology of the cell, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 152 citations in OpenAlex.
- Similarities and Differences in the Pattern of Tau Hyperphosphorylation in Physiological and Pathological Conditions: Impacts on the Elaboration of Therapies to Prevent Tau Pathology.Frontiers in neurology · 2020Pooled it
- Tau-Targeted Therapeutic Strategies: Mechanistic Targets, Clinical Pipelines, and Analysis of Failures.Cells · 2025Review
- Conformational signatures induced by ubiquitin modification in the amyloid-forming tau repeat domain.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A pathological phosphorylation pattern enhances tau cooperativity on microtubules and facilitates tau filament assembly.Research square · 2025Article
- GSK3β phosphorylation catalyzes the aggregation of tau into Alzheimer's disease-like filaments.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Phosphorylation of tau at a single residue inhibits binding to the E3 ubiquitin ligase, CHIP.Nature communications · 2024Article
- Site-specific phosphorylation of tau impacts mitochondrial function and response to stressors.Journal of neurochemistry · 2024Article
- Modulation of Tau Pathology in Alzheimer's Disease by Dietary Bioactive Compounds.International journal of molecular sciences · 2024Review
- Untangling Tau: Molecular Insights into Neuroinflammation, Pathophysiology, and Emerging Immunotherapies.Current issues in molecular biology · 2023Review
- Site-specific phosphorylation of tau impacts mitochondrial biology and response to stressors.bioRxiv : the preprint server for biology · 2023Article
- The Implication of Glial Metabotropic Glutamate Receptors in Alzheimer's Disease.Current neuropharmacology · 2023Review
- Oxidative Stress in Tauopathies: From Cause to Therapy.Antioxidants (Basel, Switzerland) · 2022Review
- The propagation mechanisms of extracellular tau in Alzheimer's disease.Journal of neurology · 2022Review
- β-arrestin1 promotes tauopathy by transducing GPCR signaling, disrupting microtubules and autophagy.Life science alliance · 2022Article
- Tau Post-Translational Modifications: Potentiators of Selective Vulnerability in Sporadic Alzheimer's Disease.Biology · 2021Review
- Article
- Protein Aggregation Landscape in Neurodegenerative Diseases: Clinical Relevance and Future Applications.International journal of molecular sciences · 2021Review
- Mechanisms of Regulation and Diverse Activities of Tau-Tubulin Kinase (TTBK) Isoforms.Cellular and molecular neurobiology · 2021Article
- Antisense Oligonucleotide-Mediated Reduction of HDAC6 Does Not Reduce Tau Pathology in P301S Tau Transgenic Mice.Frontiers in neurology · 2021Article
- A combinatorial native MS and LC-MS/MS approach reveals high intrinsic phosphorylation of human Tau but minimal levels of other key modifications.The Journal of biological chemistry · 2020Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The differentiation of neurons and the outgrowth of neurites depends on microtubule-associated proteins such as tau protein. To study this process, we have used the model of Sf9 cells, which allows efficient transfection with microtubule-associated proteins (via baculovirus vectors) and observation of the resulting neurite-like extensions. We compared the phosphorylation of tau23 (the embryonic form of human tau) with mutants in which critical phosphorylation sites were deleted by mutating Ser or Thr residues into Ala. One can broadly distinguish two types of sites, the KXGS motifs in the repeats (which regulate the affinity of tau to microtubules) and the SP or TP motifs in the domains flanking the repeats (which contain epitopes for antibodies diagnostic of Alzheimer's disease). Here we report that both types of sites can be phosphorylated by endogenous kinases of Sf9 cells, and that the phosphorylation pattern of the transfected tau is very similar to that of neurons, showing that Sf9 cells can be regarded as an approximate model for the neuronal balance between kinases and phosphatases. We show that mutations in the repeat domain and in the flanking domains have opposite effects. Mutations of KXGS motifs in the repeats (Ser262, 324, and 356) strongly inhibit the outgrowth of cell extensions induced by tau, even though this type of phosphorylation accounts for only a minor fraction of the total phosphate. This argues that the temporary detachment of tau from microtubules (by phosphorylation at KXGS motifs) is a necessary condition for establishing cell polarity at a critical point in space or time. Conversely, the phosphorylation at SP or TP motifs represents the majority of phosphate (>80%); mutations in these motifs cause an increase in cell extensions, indicating that this type of phosphorylation retards the differentiation of the cells.
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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.