Characterization of Neuronal Tau Protein ...
Document type :
Article dans une revue scientifique
DOI :
Permalink :
Title :
Characterization of Neuronal Tau Protein as a Target of Extracellular Signal-regulated Kinase
Author(s) :
Qi, Haoling [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Prabakaran, Sudhakaran [Auteur]
Harvard Medical School [Boston] [HMS]
Cantrelle, Francois-Xavier [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Chambraud, Béatrice [Auteur]
Petites Molécules de neuroprotection, neurorégénération et remyélinisation
Gunawardena, Jeremy [Auteur]
Harvard Medical School [Boston] [HMS]
Lippens, Guy [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Landrieu, Isabelle [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Prabakaran, Sudhakaran [Auteur]
Harvard Medical School [Boston] [HMS]
Cantrelle, Francois-Xavier [Auteur]

Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Chambraud, Béatrice [Auteur]
Petites Molécules de neuroprotection, neurorégénération et remyélinisation
Gunawardena, Jeremy [Auteur]
Harvard Medical School [Boston] [HMS]
Lippens, Guy [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Landrieu, Isabelle [Auteur]

Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Journal title :
THE JOURNAL OF BIOLOGICAL CHEMISTRY
Volume number :
291
Pages :
7742-7753
Publication date :
2016-04-01
ISSN :
0021-9258, 1083-351X
English keyword(s) :
Alzheimer disease
extracellular signal-regulated kinase (ERK)
nuclear magnetic resonance (NMR)
protein phosphorylation
protein-protein interaction
Tau protein (Tau)
extracellular signal-regulated kinase (ERK)
nuclear magnetic resonance (NMR)
protein phosphorylation
protein-protein interaction
Tau protein (Tau)
HAL domain(s) :
Chimie/Chimie théorique et/ou physique
English abstract : [en]
Tau neuronal protein has a central role in neurodegeneration and is implicated in Alzheimer disease development. Abnormal phosphorylation of Tau impairs its interaction with other proteins and is associated with its ...
Show more >Tau neuronal protein has a central role in neurodegeneration and is implicated in Alzheimer disease development. Abnormal phosphorylation of Tau impairs its interaction with other proteins and is associated with its dysregulation in pathological conditions. Molecular mechanisms leading to hyperphosphorylation of Tau in pathological conditions are unknown. Here, we characterize phosphorylation of Tau by extracellular-regulated kinase (ERK2), a mitogen-activated kinase (MAPK) that responds to extracellular signals. Analysis of in vitro phosphorylated Tau by activated recombinant ERK2 with nuclear magnetic resonance spectroscopy (NMR) reveals phosphorylation of 15 Ser/Thr sites. In vitro phosphorylation of Tau using rat brain extract and subsequent NMR analysis identifies the same sites. Phosphorylation with rat brain extract is known to transform Tau into an Alzheimer disease-like state. Our results indicate that phosphorylation of Tau by ERK2 alone is sufficient to produce the same characteristics. We further investigate the mechanism of ERK2 phosphorylation of Tau. Kinases are known to recognize their protein substrates not only by their specificity for a targeted Ser or Thr phosphorylation site but also by binding to linear-peptide motifs called docking sites. We identify two main ERK2 docking sites in Tau sequence using NMR. Our results suggest that ERK2 dysregulation in Alzheimer disease could lead to abnormal phosphorylation of Tau resulting in the pathology of the disease.Show less >
Show more >Tau neuronal protein has a central role in neurodegeneration and is implicated in Alzheimer disease development. Abnormal phosphorylation of Tau impairs its interaction with other proteins and is associated with its dysregulation in pathological conditions. Molecular mechanisms leading to hyperphosphorylation of Tau in pathological conditions are unknown. Here, we characterize phosphorylation of Tau by extracellular-regulated kinase (ERK2), a mitogen-activated kinase (MAPK) that responds to extracellular signals. Analysis of in vitro phosphorylated Tau by activated recombinant ERK2 with nuclear magnetic resonance spectroscopy (NMR) reveals phosphorylation of 15 Ser/Thr sites. In vitro phosphorylation of Tau using rat brain extract and subsequent NMR analysis identifies the same sites. Phosphorylation with rat brain extract is known to transform Tau into an Alzheimer disease-like state. Our results indicate that phosphorylation of Tau by ERK2 alone is sufficient to produce the same characteristics. We further investigate the mechanism of ERK2 phosphorylation of Tau. Kinases are known to recognize their protein substrates not only by their specificity for a targeted Ser or Thr phosphorylation site but also by binding to linear-peptide motifs called docking sites. We identify two main ERK2 docking sites in Tau sequence using NMR. Our results suggest that ERK2 dysregulation in Alzheimer disease could lead to abnormal phosphorylation of Tau resulting in the pathology of the disease.Show less >
Language :
Anglais
Audience :
Non spécifiée
ANR Project :
Administrative institution(s) :
CNRS
Université de Lille
Université de Lille
Research team(s) :
RMN et interactions moléculaires
Submission date :
2020-02-12T15:44:53Z
2021-04-23T13:15:44Z
2021-04-23T13:15:44Z
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