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Accurate MS-based Rab10 Phosphorylation Stoichiometry Determination as Readout for LRRK2 Activity in Parkinson's Disease
Authors: zge Karayel  Francesca Tonelli  Sebastian Virreira Winter  Phillip E Geyer  Ying Fan  Esther M Sammler  Dario R Alessi  Martin Steger  Matthias Mann
Institution:1. Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany;2. Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, United Kingdom;3. Department of Neurology, School of Medicine, Ninewells Hospital, Ninewells Drive, Dundee, United Kingdom
Abstract:
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  • Highlights
    • ?MS-based clinical assay that accurately determines phospho Rab10 occupancy.
    • ?Stable isotope labeled phosphopeptide injected as a standard with endogenous tryptic phospho Rab peptide for accurate ratio determination.
    • ?Determination of pRab levels in neutrophils of Parkinson disease patients.
    • ?Relevance of pRab levels as marker of PD.
    Keywords:Biomarker: diagnostic  clinical proteomics  neurodegenerative diseases  parallel reaction monitoring  Parkinson disease  phosphorylation  protein kinases  targeted mass spectrometry  targeted therapies  selected ion monitoring
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