Novel screening cascade identifies MKK4 as key kinase regulating Tau phosphorylation at Ser422
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- Grueninger, F., Bohrmann, B., Christensen, K. et al. Mol Cell Biochem (2011) 357: 199. doi:10.1007/s11010-011-0890-6
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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.