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MARQUIS: A multiplex method for absolute quantification of peptides and posttranslational modifications

Author(s)
Curran, Timothy G.; Zhang, Yi; Ma, Daniel J.; Sarkaria, Jann N.; White, Forest M.
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Abstract
Absolute quantification of protein expression and posttranslational modifications by mass spectrometry has been challenging due to a variety of factors, including the potentially large dynamic range of phosphorylation response. To address these issues, we have developed MARQUIS—Multiplex Absolute Regressed Quantification with Internal Standards—a novel mass spectrometry-based approach using a combination of isobaric tags and heavy-labelled standard peptides, to construct internal standard curves for peptides derived from key nodes in signal transduction networks. We applied MARQUIS to quantify phosphorylation dynamics within the ​EGFR network at multiple time points following stimulation with several ligands, enabling a quantitative comparison of ​EGFR phosphorylation sites and demonstrating that receptor phosphorylation is qualitatively similar but quantitatively distinct for each ​EGFR ligand tested. MARQUIS was also applied to quantify the effect of ​EGFR kinase inhibition on glioblastoma patient-derived xenografts. MARQUIS is a versatile method, broadly applicable and extendable to multiple mass spectrometric platforms.
Date issued
2015-01
URI
http://hdl.handle.net/1721.1/99545
Department
Massachusetts Institute of Technology. Department of Biological Engineering; Koch Institute for Integrative Cancer Research at MIT
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Curran, Timothy G., Yi Zhang, Daniel J. Ma, Jann N. Sarkaria, and Forest M. White. “MARQUIS: A Multiplex Method for Absolute Quantification of Peptides and Posttranslational Modifications.” Nat Comms 6 (January 12, 2015): 5924.
Version: Author's final manuscript
ISSN
2041-1723

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