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

Erik L. De Graaf; Joanna Kaplon; Shabaz Mohammed; Lisette A M Vereijken; Daniel P. Duarte; Laura Redondo Gallego; Albert J R Heck; Daniel S. Peeper; A. F Maarten Altelaar

doi:10.1021/acs.jproteome.5b00236

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

Erik L. De Graaf, Joanna Kaplon, Shabaz Mohammed, Lisette A M Vereijken, Daniel P. Duarte, Laura Redondo Gallego, Albert J R Heck^*, Daniel S. Peeper, A. F Maarten Altelaar^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	2906-2914
Number of pages	9
Journal	Journal of Proteome Research
Volume	14
Issue number	7
DOIs	https://doi.org/10.1021/acs.jproteome.5b00236
Publication status	Published - 2 Jul 2015

Keywords

ERK1/2
MAPK
mTOR
network biology
pathway
phosphoproteomics
PI3K
RPS6
signal transduction
SRM
Ti-IMAC

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10.1021/acs.jproteome.5b00236

SenescenceFinal published version, 2.51 MBLicence: Taverne

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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, 14(7), 2906-2914. https://doi.org/10.1021/acs.jproteome.5b00236

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

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",

author = "{De Graaf}, {Erik L.} and Joanna Kaplon and Shabaz Mohammed and Vereijken, {Lisette A M} and Duarte, {Daniel P.} and {Redondo Gallego}, Laura and Heck, {Albert J R} and Peeper, {Daniel S.} and Altelaar, {A. F Maarten}",

year = "2015",

month = jul,

day = "2",

doi = "10.1021/acs.jproteome.5b00236",

language = "English",

volume = "14",

pages = "2906--2914",

journal = "Journal of Proteome Research",

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AU - De Graaf, Erik L.

AU - Kaplon, Joanna

AU - Mohammed, Shabaz

AU - Vereijken, Lisette A M

AU - Duarte, Daniel P.

AU - Redondo Gallego, Laura

AU - Heck, Albert J R

AU - Peeper, Daniel S.

AU - Altelaar, A. F Maarten

PY - 2015/7/2

Y1 - 2015/7/2

N2 - 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.

AB - 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.

KW - ERK1/2

KW - MAPK

KW - mTOR

KW - network biology

KW - pathway

KW - phosphoproteomics

KW - PI3K

KW - RPS6

KW - signal transduction

KW - SRM

KW - Ti-IMAC

UR - http://www.scopus.com/inward/record.url?scp=84947295308&partnerID=8YFLogxK

U2 - 10.1021/acs.jproteome.5b00236

DO - 10.1021/acs.jproteome.5b00236

M3 - Article

C2 - 26011226

AN - SCOPUS:84947295308

SN - 1535-3893

VL - 14

SP - 2906

EP - 2914

JO - Journal of Proteome Research

JF - Journal of Proteome Research

IS - 7

ER -

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

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Keywords

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