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FLEXIQinase, a mass spectrometry-based assay, to unveil multi-kinase mechanisms

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2013

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Singh, Sasha, Dominic Winter, Parizad M. Bilimoria, Azad Bonni, Hanno Steen, and Judith A. Steen. 2013. FLEXIQinase, a mass spectrometry-based assay, to unveil multi-kinase mechanisms. Nature Methods 9(5): 504-508.

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Abstract

We introduce a mass spectrometry-based method that provides residue-resolved quantitative information about protein phosphorylation. In this FLEXIQinase assay we combined our Full-Length Expressed Stable Isotope-labeled Protein for Quantification strategy (FLEXIQuant) with a traditional kinase assay to determine the mechanisms of multi-kinase substrate phosphorylation such as priming-dependent kinase activities. The assay monitors the decrease in signal intensity of the substrate peptides and the concomitant increase in the (n×80 Da)-shifted phosphorylated peptide. We analyzed the c-Jun N-terminal Kinase (JNK)-dependent glycogen synthase kinase 3β (GSK3β) activity on doublecortin (DCX) revealing mechanistic details about the role of phosphorylation cross-talk in GSK3β activity and permitting an advanced model for GSK3β-mediated signaling.

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in vitro, phosphorylation, quantitative proteomics, mass spectrometry, full length stable isotope labeled protein standards

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