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

Autor: Grueninger, Fiona, Bohrmann, Bernd, Christensen, Klaus, Graf, Martin, Roth, Doris, Czech, Christian
Zdroj: Molecular & Cellular Biochemistry; Nov2011, Vol. 357 Issue 1/2, p199-207, 9p
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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