Characterization of Neuronal Tau Protein ...
Type de document :
Article dans une revue scientifique
DOI :
URL permanente :
Titre :
Characterization of Neuronal Tau Protein as a Target of Extracellular Signal-regulated Kinase
Auteur(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]
Titre de la revue :
THE JOURNAL OF BIOLOGICAL CHEMISTRY
Numéro :
291
Pagination :
7742-7753
Date de publication :
2016-04-01
ISSN :
0021-9258, 1083-351X
Mot(s)-clé(s) en anglais :
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)
Discipline(s) HAL :
Chimie/Chimie théorique et/ou physique
Résumé en anglais : [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 ...
Lire la suite >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.Lire moins >
Lire la suite >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.Lire moins >
Langue :
Anglais
Audience :
Non spécifiée
Projet ANR :
Établissement(s) :
CNRS
Université de Lille
Université de Lille
Équipe(s) de recherche :
RMN et interactions moléculaires
Date de dépôt :
2020-02-12T15:44:53Z
2021-04-23T13:15:44Z
2021-04-23T13:15:44Z
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