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Cited by 515Alzheimer's disease research and treatmentsProtein Kinase Regulation and GTPase SignalingDementia and Cognitive Impairment Research

Glycogen synthase kinase‐3 and the Alzheimer‐like state of microtubule‐associated protein tau

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Mandelkow, E.-M., Drewes, G., Biernat, J., Gustke, N., Van Lint, J., Vandenheede, J.R., Mandelkow, E.·1992·FEBS Letters
DOI 10.1016/0014-5793(92)81496-9
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Abstract

The Alzheimer‐like state of tau protein includes phosphorylation by a proline‐directed Ser/Thr kinase present in normal or pathological human brain. Extending earlier results on MAP kinase, we show here that the proline‐directed kinase, GSK3, can induce an Alzheimer‐like immune response involving several distinct and phoshorylatable epitopes at Ser—Pro motifs, as well as gel mobility shift, similar to MAP kinase. Both kinases behave like microtubule‐associated proteins in that they co‐purify through cycles of assembly and disassembly, and both kinases are directly associated with paired helical filaments.

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Crossref · 10.1016/0014-5793(92)81496-9

Cites

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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 [12]

    The Introduction and section 3.1 support in-vitro phosphorylation of tau by MAP kinase and GSK3 and describe Alzheimer-like phosphorylation. They do not establish the claim for neuronal cdc2-like kinase (cdk5): the Introduction instead discusses cell-cycle cdc2, reporting only slight phosphorylation and no Alzheimer-like immune response. Page numbers are unavailable in our copy. (LLM, conf=0.89)

    Experimental — accuracy not yet measured

  • Prior 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 [12]

    The discussion (p. 56) says tau phosphorylation by several common kinases has been studied in vitro and that whether those modifications occur in vivo remains uncertain. It does not establish the stronger claim that every study of tau phosphorylation by the kinases in question was carried out in vitro. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • GSK3β probably was directly responsible for the increased immunoreactivities and mobility shifts observed, because in vitro studies demonstrated that tau can be directly phosphorylated by GSK3β at many of the same sites.

    “However, since in vitro studies [7,12,14] have demonstrated that tau can be directly phosphorylated by GSK3fl at many of the sites we observed in transfected cells, GSK3fl probably was directly responsible for the increased immunoreactivities and mobility shifts observed here.”

    From Glycogen synthase kinase-3β phosphorylates tau protein at multiple sites in intact cells (1995) · cites this paper as [12]

  • The results extend in vitro findings to an in vivo model system and indicate that GSK3β may be involved in tau phosphorylation in vivo.

    “They extend results obtained in vitro [7,12,14] to an in vivo model system, and indicate that GSK3fl may be involved in the phosphorylation of tau in vivo.”

    From Glycogen synthase kinase-3β phosphorylates tau protein at multiple sites in intact cells (1995) · cites this paper as [12]

  • par-1 and shaggy are known tau kinases.

    “Two modifiers identified in an unbiased manner from these screens, par-1 and shaggy, are known tau kinases (24,25,90–92)”

    From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [25]

    The Introduction and Results report that GSK3 phosphorylates tau, but our copy does not identify GSK3 as shaggy or discuss par-1 as a tau kinase. Searches for “shaggy,” “par-1,” and a Drosophila GSK3 homolog found no passage establishing either named modifier as a tau kinase. (LLM, conf=0.76)

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Cites

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Research works printed but not linked: 6

  1. Lichtenberg-Kraag, B., Mandelkow, E.-M., Biernat, J., Steiner, B., Schrbter, C., Gustke, N.. Meyer, H.E. ond Mandelkow. E. (1992) Proc. Natl. Acad. Sci. USA 89, 53845388.
  2. Goedcrt, M., Wischik, C., Crowther, R., Walker, J. and Klug, A. (1988) Proc. Natl. Acad. Sci. USA 85, 40514055.
  3. ISj Van Lint, J., Khnndelwal, R.L., Merlevede, W. and Vandens hccdc, J.R, (1993) Anal. Biochem. (in press). 11Gl [l71
  4. I Stcrnbcrgcr, N.H., Sternbcrger, L.A. and Ulrich, 5. (1985) Proc. Natl. Acad. Sci. USA 82, 4274X?76.
  5. Grundke-lqbal, l., Tqbal, K.. 'rung, Y., Quinlan, M., Wisnicwski, M. and Binder, L. (198G) Proc. Natl. Asad. Sci. USA 83, 4913- 4917.
  6. Vincent, I.J. and Davies. P. (1992) Proc. Natl. Acad. Sci. USA 89.2878-2882.

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Authors
Mandelkow, E.-M., Drewes, G., Biernat, J., Gustke, N., Van Lint, J., Vandenheede, J. R., & Mandelkow, E.
Affiliations
  • Deutsches Elektronen-Synchrotron DESY (DE)
  • KU Leuven (BE)
ORCID
Venue
FEBS Letters
Publisher
Wiley
Published
1992-12-21
Volume
314
Issue
3
Pages
315-321
ISSN
  • 0014-5793 (ISSN-L)
  • 1873-3468
DOI
10.1016/0014-5793(92)81496-9
OpenAlex
W1983769449
Cited by
515
References
2
Citations by year
2026: 3 · 2025: 4 · 2024: 5 · 2023: 8 · 2022: 8 · 2021: 3 · 2020: 11 · 2019: 6 · 2018: 6 · 2017: 8 · 2016: 9 · 2015: 7 · 2014: 10 · 2013: 11 · 2012: 18
FWCI
18.83
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 3283 d)
Locations
  • FEBS Letters (publishedVersion)
  • PubMed (publishedVersion)
  • DESY Publication Database (PUBDB) (Deutsches Elektronen-Synchrotron) (submittedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
glycogen synthase kinase-3, tau protein, Alzheimer's disease, tau phosphorylation, mitogen-activated protein kinase, paired helical filaments, microtubule-associated proteins, immune response, gel mobility shift
MeSH terms
Alzheimer Disease, Animals, Cattle, Cloning, Molecular, Humans, Intermediate Filaments, Kinetics, Microtubules, Phosphorylation, Protein Kinases, tau Proteins, Calcium-Calmodulin-Dependent Protein Kinases, Glycogen Synthase Kinases

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