363 441

Cited 142 times in

DYRK1A-mediated hyperphosphorylation of Tau. A functional link between Down syndrome and Alzheimer disease

Authors
 Soo-Ryoon Ryoo  ;  Hey Kyeong Jeong  ;  Woo-Joo Song  ;  Sul-Hee Chung  ;  Young Soo Ahn  ;  Young-Hee Cheon  ;  In-Sook Kim  ;  Hye-Won Lee  ;  Hyun-Jeong Cho  ;  Jin-Ju Yoo  ;  Chinzorig Radnaabazar 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.282(48) : 34850-34857, 2007 
Journal Title
 JOURNAL OF BIOLOGICAL CHEMISTRY 
ISSN
 0021-9258 
Issue Date
2007
MeSH
Alzheimer Disease/genetics* ; Animals ; Brain/metabolism ; Cell Line ; DNA, Complementary/metabolism ; Down Syndrome/genetics* ; Humans ; Immunohistochemistry ; Mice ; Mice, Transgenic ; Models, Biological ; Phosphorylation ; Protein-Serine-Threonine Kinases/genetics* ; Protein-Serine-Threonine Kinases/physiology* ; Protein-Tyrosine Kinases/genetics* ; Protein-Tyrosine Kinases/physiology* ; Recombinant Proteins/chemistry ; Serine/chemistry ; Threonine/chemistry ; tau Proteins/chemistry*
Abstract
Most individuals with Down syndrome show early onset of Alzheimer disease (AD), resulting from the extra copy of chromosome 21. Located on this chromosome is a gene that encodes the dual specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). One of the pathological hallmarks in AD is the presence of neurofibrillary tangles (NFTs), which are insoluble deposits that consist of abnormally hyperphosphorylated Tau. Previously it was reported that Tau at the Thr-212 residue was phosphorylated by Dyrk1A in vitro. To determine the physiological significance of this phosphorylation, an analysis was made of the amount of phospho-Thr-212-Tau (pT212) in the brains of transgenic mice that overexpress the human DYRK1A protein (DYRK1A TG mice) that we recently generated. A significant increase in the amount of pT212 was found in the brains of DYRK1A transgenic mice when compared with age-matched littermate controls. We further examined whether Dyrk1A phosphorylates other Tau residues that are implicated in NFTs. We found that Dyrk1A also phosphorylates Tau at Ser-202 and Ser-404 in vitro. Phosphorylation by Dyrk1A strongly inhibited the ability of Tau to promote microtubule assembly. Following this, using mammalian cells and DYRK1A TG mouse brains, it was demonstrated that the amounts of phospho-Ser-202-Tau and phospho-Ser-404-Tau are enhanced when DYRK1A amounts are high. These results provide the first in vivo evidence for a physiological role of DYRK1A in the hyperphosphorylation of Tau and suggest that the extra copy of the DYRK1A gene contributes to the early onset of AD
Files in This Item:
T200701337.pdf Download
DOI
10.1074/jbc.M707358200
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, In Sook(김인숙)
Ahn, Young Soo(안영수)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/96226
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links