Novel screening cascade identifies MKK4 as key kinase regulating Tau phosphorylation at Ser422

  • Fiona Grueninger
  • Bernd Bohrmann
  • Klaus Christensen
  • Martin Graf
  • Doris Roth
  • Christian Czech
Article

Abstract

Phosphorylation of Tau at serine 422 promotes Tau aggregation. The kinase that is responsible for this key phosphorylation event has so far not been identified but could be a potential drug target for Alzheimer’s disease. We describe here an assay strategy to identify this kinase. Using a combination of screening a library of 65’000 kinase inhibitors and in vitro inhibitor target profiling of the screening hits using the Ambit kinase platform, MKK4 was identified as playing a key role in Tau-S422 phosphorylation in human neuroblastoma cells.

Keywords

MKK4 Alzheimer’s disease Tau phosphorylation 

Supplementary material

11010_2011_890_MOESM1_ESM.pptx (88 kb)
Supplementary material 1 (PPTX 88 kb)
11010_2011_890_MOESM2_ESM.pptx (71 kb)
Supplementary material 2 (PPTX 70 kb)
11010_2011_890_MOESM3_ESM.xls (81 kb)
Supplementary material 3 (XLS 81 kb)

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Fiona Grueninger
    • 1
  • Bernd Bohrmann
    • 1
  • Klaus Christensen
    • 2
  • Martin Graf
    • 2
  • Doris Roth
    • 2
  • Christian Czech
    • 1
  1. 1.CNS Discovery and Translation Pharma Research and Exploratory DevelopmentF. Hoffmann-La Roche AGBaselSwitzerland
  2. 2.Discovery Technologies Pharma Research and Exploratory DevelopmentF. Hoffmann-La Roche AGBaselSwitzerland

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