MISC

2009年1月

Phosphorylation of tau at Ser214 mediates its interaction with 14-3-3 protein: implications for the mechanism of tau aggregation

JOURNAL OF NEUROCHEMISTRY
  • Golam Sadik
  • ,
  • Toshihisa Tanaka
  • ,
  • Kiyoko Kato
  • ,
  • Hidenaga Yamamori
  • ,
  • Begum Nurun Nessa
  • ,
  • Takashi Morihara
  • ,
  • Masatoshi Takeda

108
1
開始ページ
33
終了ページ
43
記述言語
英語
掲載種別
DOI
10.1111/j.1471-4159.2008.05716.x
出版者・発行元
WILEY-BLACKWELL PUBLISHING, INC

The microtubule associated protein tau is a major component of neurofibrillary tangles in Alzheimer disease brain, however the neuropathological processes behind the formation of neurofibrillary tangles are still unclear. Previously, 14-3-3 proteins were reported to bind with tau. 14-3-3 Proteins usually bind their targets through specific serine/threonine -phosphorylated motifs. Therefore, the interaction of tau with 14-3-3 mediated by phosphorylation was investigated. In this study, we show that the phosphorylation of tau by either protein kinase A (PKA) or protein kinase B (PKB) enhances the binding of tau with 14-3-3 in vitro. The affinity between tau and 14-3-3 is increased 12- to 14-fold by phosphorylation as determined by real time surface plasmon resonance studies. Mutational analyses revealed that Ser214 is critical for the phosphorylation-mediated interaction of tau with 14-3-3. Finally, in vitro aggregation assays demonstrated that phosphorylation by PKA/PKB inhibits the formation of aggregates/filaments of tau induced by 14-3-3. As the phosphorylation at Ser214 is up-regulated in fetal brain, tau's interaction with 14-3-3 may have a significant role in the organization of the microtubule cytoskeleton in development. Also as the phosphorylation at Ser214 is up-regulated in Alzheimer's disease brain, tau's interaction with 14-3-3 might be involved in the pathology of this disease.

Web of Science ® 被引用回数 : 60

リンク情報
DOI
https://doi.org/10.1111/j.1471-4159.2008.05716.x
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000261441500004&DestApp=WOS_CPL

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