Zinc stimulates tau S214 phosphorylation by the activation of Raf/mitogen-activated protein kinase-kinase/extracellular signal-regulated kinase pathway

Insook Kim, Eun Ji Park, Jeho Seo, Suk Jin Ko, Jinu Lee, Chul Hoon Kim

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Hyperphosphorylated tau is a main component of neurofibrillary tangles, a pathological hallmark of Alzheimer's disease (AD). There is evidence that various protein kinases are involved in tau hyperphosphorylation. However, little is known about AD-related stimuli that activates tau kinases. We investigated the role of zinc, a metal involved in AD pathology, in tau phosphorylation. Zinc increased the phosphorylation of serine 214 (S214) in tau protein in human wild-type tau1-441-expressing SH-SY5Y cells. The phosphorylation was inhibited by suppressing the Ras-Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (ERK) pathway. Mutation of serine to alanine at residue 214 of tau reduced microtubule polymerization impairment by ERK phosphorylation. These data suggest that zinc induces S214 phosphorylation in tau through ERK activation and interferes with microtubule polymerization.

Original languageEnglish
Pages (from-to)839-844
Number of pages6
JournalNeuroReport
Volume22
Issue number16
DOIs
Publication statusPublished - 2011 Nov 16

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Mitogen-Activated Protein Kinase Kinases
Extracellular Signal-Regulated MAP Kinases
Serine
Zinc
Phosphorylation
Alzheimer Disease
Microtubules
Polymerization
Neurofibrillary Tangles
Alanine
Protein Kinases
Phosphotransferases
Metals
Pathology
Mutation

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Kim, Insook ; Park, Eun Ji ; Seo, Jeho ; Ko, Suk Jin ; Lee, Jinu ; Kim, Chul Hoon. / Zinc stimulates tau S214 phosphorylation by the activation of Raf/mitogen-activated protein kinase-kinase/extracellular signal-regulated kinase pathway. In: NeuroReport. 2011 ; Vol. 22, No. 16. pp. 839-844.
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Zinc stimulates tau S214 phosphorylation by the activation of Raf/mitogen-activated protein kinase-kinase/extracellular signal-regulated kinase pathway. / Kim, Insook; Park, Eun Ji; Seo, Jeho; Ko, Suk Jin; Lee, Jinu; Kim, Chul Hoon.

In: NeuroReport, Vol. 22, No. 16, 16.11.2011, p. 839-844.

Research output: Contribution to journalArticle

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