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SCIENTIFIC LITERATURE · MED

Detection of endogenous S1292 LRRK2 autophosphorylation in mouse tissue as a readout for kinase activity.

NPJ Parkinsons Dis · 2018-04-19

DOI: 10.1038/s41531-018-0049-1PMID: 29707617

Open accessresearch-article; Journal ArticleOriginal source ↗

Research overview

The text below is the source article’s original abstract under a verified reuse license. cc by

Parkinson's disease-linked mutations in LRRK2 enhance the kinase activity of the protein, therefore targeting LRRK2 kinase activity is a promising therapeutic approach. Phosphorylation at S935 of LRRK2 and of its Rab GTPase substrates have proven very useful biomarkers to monitor its kinase activity. Complementary to these approaches autophosphorylation of LRRK2 can be used as a direct kinase activity readout but to date detection of autophosphorylation at endogenous levels in vivo has been limited. We developed a fractionation-based enrichment method to successfully detect endogenous S1292 LRRK2 autophosphorylation in mouse tissues and highlight S1292 as a physiological readout candidate for LRRK2 kinase activity in vivo.

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