p42 map kinase phosphorylation sites in microtubule‐associated protein tau are dephosphorylated by protein phosphatase 2A1 Implications for Alzheimer's disease
Open accessAbstract
The paired helical filament (PHF), which comprises the major fibrous element of the neurofibrillary tangle of Alzheimer's disease, is composed of abnormally phosphorylated microtubule‐associated protein tau. Here we show that p42 MAP kinase phosphorylates recombinant tau and converts it to a form which is similar to PHF tau. Of the major serine/threonine protein phosphatases found in mammalian tissues only protein phosphatase 2A (PP2A) could dephosphorylate tau phosphorylated in this manner, with PP2A 1 being the most effective form of the enzyme.
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MAP kinase, GSK3, and neuronal cdc2-like kinase (cdk5) have been shown to phosphorylate tau in vitro at sites that are phosphorylated in PHFs.
“Mitogen-activated protein kinase, glycogen synthase kinase-3 (GSK3) and neuronal cdc2-1ike kinase have been shown to phosphorylate tau protein in vitro at a number of sites that are phosphorylated in PHFs.”
From Glycogen synthase kinase-3β phosphorylates tau protein at multiple sites in intact cells (1995) · cites this paper as [4]
The Discussion reports that p42 MAP kinase phosphorylates tau at sites abnormally phosphorylated in PHF tau. The Introduction also mentions other tau-phosphorylating kinases, but our copy does not identify them as GSK3 or neuronal cdc2-like kinase or establish the claimed result for those two enzymes. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPrior studies of tau phosphorylation by these kinases were carried out in vitro without exception.
“However, without exception, these studies have been carried out in vitro.”
From Glycogen synthase kinase-3β phosphorylates tau protein at multiple sites in intact cells (1995) · cites this paper as [4]
The Introduction describes prior work in which a kinase purified from pig brain phosphorylated recombinant tau, and Methods §2.2 describes this paper’s phosphorylation assay using isolated tau and kinase. These passages support an in-vitro characterization, but the paper does not establish that every prior study of tau phosphorylation by the kinases was conducted in vitro. The indexed copy provides section labels but no page numbers for these passages. (LLM, conf=0.82)
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- Authors
- Goedert, M., Cohen, E. S., Jakes, R., & Cohen, P.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- University of Dundee (GB)
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 1992-11-02
- Volume
- 312
- Issue
- 1
- Pages
- 95-99
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2016877136
- Cited by
- 272
- References
- 3
- Citations by year
- 2023: 2 · 2022: 3 · 2021: 5 · 2020: 2 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 2 · 2015: 5 · 2014: 4 · 2013: 8 · 2012: 3
- FWCI
- 14.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion, other-oa)
- Funders
- Royal Society
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- tau protein, p42 MAP kinase, protein phosphorylation, protein dephosphorylation, protein phosphatase 2A, neurofibrillary tangles, Alzheimer's disease, microtubule-associated proteins
- MeSH terms
- Brain, Calcium, Cloning, Molecular, Electrophoresis, Polyacrylamide Gel, Ethers, Cyclic, Humans, Kinetics, Magnesium, Phosphoprotein Phosphatases, Phosphorylation, Protein Kinases, Recombinant Proteins, tau Proteins, Calcium-Calmodulin-Dependent Protein Kinases, Okadaic Acid, Protein Phosphatase 2
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