Signal Transduction Reaction Monitoring Deciphers Site-Specific PI3K-mTOR/MAPK Pathway Dynamics in Oncogene-Induced Senescence

We report a straightforward strategy to comprehensively monitor signal transduction pathway dynamics in mammalian systems. Combining targeted quantitative proteomics with highly selective phosphopeptide enrichment, we monitor, with great sensitivity, phosphorylation dynamics of the PI3K-mTOR and MAP...

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Bibliographic Details
Published in:Journal of proteome research 2015-07, Vol.14 (7), p.2906-2914
Main Authors: de Graaf, Erik L, Kaplon, Joanna, Mohammed, Shabaz, Vereijken, Lisette A. M, Duarte, Daniel P, Redondo Gallego, Laura, Heck, Albert J. R, Peeper, Daniel S, Altelaar, A. F. Maarten
Format: Article
Language:English
Subjects:
Cell Line
Cellular Senescence - genetics
Humans
MAP Kinase Signaling System
Oncogenes
Phosphatidylinositol 3-Kinases - metabolism
Phosphorylation
Signal Transduction
TOR Serine-Threonine Kinases - metabolism
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Summary:We report a straightforward strategy to comprehensively monitor signal transduction pathway dynamics in mammalian systems. Combining targeted quantitative proteomics with highly selective phosphopeptide enrichment, we monitor, with great sensitivity, phosphorylation dynamics of the PI3K-mTOR and MAPK signaling networks. Our approach consists of a single enrichment step followed by a single targeted proteomics experiment, circumventing the need for labeling and immune purification while enabling analysis of selected phosphorylation nodes throughout signaling pathways. The need for such a comprehensive pathway analysis is illustrated by highlighting previously uncharacterized phosphorylation changes in oncogene-induced senescence, associated with diverse biological phenotypes and pharmacological intervention of the PI3K-mTOR pathway.
ISSN:1535-3893
1535-3907
DOI:10.1021/acs.jproteome.5b00236