Molecular and Cellular Biochemistry

, 357:199

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

DOI: 10.1007/s11010-011-0890-6

Cite this article as:
Grueninger, F., Bohrmann, B., Christensen, K. et al. Mol Cell Biochem (2011) 357: 199. doi:10.1007/s11010-011-0890-6

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

MKK4Alzheimer’s diseaseTau 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)

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