Signal Transduction Reaction Monitoring Deciphers Site-Specific PI3K-mTOR/MAPK Pathway Dynamics in Oncogene-Induced Senescence
Publication date
2015-07-02
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, Maarten
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Advisors
Supervisors
Document Type
Article
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Abstract
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.
Keywords
ERK1/2, MAPK, mTOR, network biology, pathway, phosphoproteomics, PI3K, RPS6, signal transduction, SRM, Ti-IMAC, Taverne, Biochemistry, General Chemistry
Citation
De Graaf, E L, Kaplon, J, Mohammed, S, Vereijken, L A M, Duarte, D P, Redondo Gallego, L, Heck, A J R, Peeper, D S & Altelaar, A F M 2015, 'Signal Transduction Reaction Monitoring Deciphers Site-Specific PI3K-mTOR/MAPK Pathway Dynamics in Oncogene-Induced Senescence', Journal of Proteome Research, vol. 14, no. 7, pp. 2906-2914. https://doi.org/10.1021/acs.jproteome.5b00236