title: Zinc stimulates tau S214 phosphorylation by the activation of Raf/mitogen-activated protein kinase-kinase/extracellular signal-regulated kinase pathway.
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.
authors.affiliation: Department of Pharmacology, Brain Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Insook
authors.initials: I
authors.lastname: Kim
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Park
authors.forename: Jeho
authors.initials: J
authors.lastname: Seo
authors.forename: Suk Jin
authors.initials: SJ
authors.lastname: Ko
authors.forename: Jinu
authors.initials: J
authors.lastname: Lee
authors.forename: Chul Hoon
authors.initials: CH
authors.lastname: Kim
mesh_terms: D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008870:Microtubules / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000502:physiology; D058105:Polymerization; D012694:Serine / Q000378:metabolism*; D015032:Zinc / Q000502:physiology*; D048490:raf Kinases / Q000378:metabolism* / Q000502:physiology; D018631:ras Proteins / Q000378:metabolism* / Q000502:physiology; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D012694:Serine; D048490:raf Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D018631:ras Proteins; D015032:Zinc