Large-Scale Phosphoproteomics Reveals Shp-2 Phosphatase-Dependent Regulators of Pdgf Receptor Signaling

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Large-Scale Phosphoproteomics Reveals Shp-2 Phosphatase-Dependent Regulators of Pdgf Receptor Signaling. / Batth, Tanveer S.; Papetti, Moreno; Pfeiffer, Anamarija; Tollenaere, Maxim A.X.; Francavilla, Chiara; Olsen, Jesper V.

In: Cell Reports, Vol. 22, No. 10, 2018, p. 2784-2796.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Batth, TS, Papetti, M, Pfeiffer, A, Tollenaere, MAX, Francavilla, C & Olsen, JV 2018, 'Large-Scale Phosphoproteomics Reveals Shp-2 Phosphatase-Dependent Regulators of Pdgf Receptor Signaling', Cell Reports, vol. 22, no. 10, pp. 2784-2796. https://doi.org/10.1016/j.celrep.2018.02.038

APA

Batth, T. S., Papetti, M., Pfeiffer, A., Tollenaere, M. A. X., Francavilla, C., & Olsen, J. V. (2018). Large-Scale Phosphoproteomics Reveals Shp-2 Phosphatase-Dependent Regulators of Pdgf Receptor Signaling. Cell Reports, 22(10), 2784-2796. https://doi.org/10.1016/j.celrep.2018.02.038

Vancouver

Batth TS, Papetti M, Pfeiffer A, Tollenaere MAX, Francavilla C, Olsen JV. Large-Scale Phosphoproteomics Reveals Shp-2 Phosphatase-Dependent Regulators of Pdgf Receptor Signaling. Cell Reports. 2018;22(10):2784-2796. https://doi.org/10.1016/j.celrep.2018.02.038

Author

Batth, Tanveer S. ; Papetti, Moreno ; Pfeiffer, Anamarija ; Tollenaere, Maxim A.X. ; Francavilla, Chiara ; Olsen, Jesper V. / Large-Scale Phosphoproteomics Reveals Shp-2 Phosphatase-Dependent Regulators of Pdgf Receptor Signaling. In: Cell Reports. 2018 ; Vol. 22, No. 10. pp. 2784-2796.

Bibtex

@article{6d78d4e2121a4d899a4f8206a003d98f,
title = "Large-Scale Phosphoproteomics Reveals Shp-2 Phosphatase-Dependent Regulators of Pdgf Receptor Signaling",
abstract = "Despite its low cellular abundance, phosphotyrosine (pTyr) regulates numerous cell signaling pathways in health and disease. We applied comprehensive phosphoproteomics to unravel differential regulators of receptor tyrosine kinase (RTK)-initiated signaling networks upon activation by Pdgf-ββ, Fgf-2, or Igf-1 and identified more than 40,000 phosphorylation sites, including many phosphotyrosine sites without additional enrichment. The analysis revealed RTK-specific regulation of hundreds of pTyr sites on key signaling molecules. We found the tyrosine phosphatase Shp-2 to be the master regulator of Pdgfr pTyr signaling. Application of a recently introduced allosteric Shp-2 inhibitor revealed global regulation of the Pdgf-dependent tyrosine phosphoproteome, which significantly impaired cell migration. In addition, we present a list of hundreds of Shp-2-dependent targets and putative substrates, including Rasa1 and Cortactin with increased pTyr and Gab1 and Erk1/2 with decreased pTyr. Our study demonstrates that large-scale quantitative phosphoproteomics can precisely dissect tightly regulated kinase-phosphatase signaling networks.",
keywords = "label-free quantitation, mass spectrometry, orbitrap, PDGF, phosphoproteomics, Q exactive, Shp-2, SHP099, TiO2, tyrosine phosphorylation",
author = "Batth, {Tanveer S.} and Moreno Papetti and Anamarija Pfeiffer and Tollenaere, {Maxim A.X.} and Chiara Francavilla and Olsen, {Jesper V.}",
note = "Copyright {\textcopyright} 2018 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2018",
doi = "10.1016/j.celrep.2018.02.038",
language = "English",
volume = "22",
pages = "2784--2796",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "10",

}

RIS

TY - JOUR

T1 - Large-Scale Phosphoproteomics Reveals Shp-2 Phosphatase-Dependent Regulators of Pdgf Receptor Signaling

AU - Batth, Tanveer S.

AU - Papetti, Moreno

AU - Pfeiffer, Anamarija

AU - Tollenaere, Maxim A.X.

AU - Francavilla, Chiara

AU - Olsen, Jesper V.

N1 - Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2018

Y1 - 2018

N2 - Despite its low cellular abundance, phosphotyrosine (pTyr) regulates numerous cell signaling pathways in health and disease. We applied comprehensive phosphoproteomics to unravel differential regulators of receptor tyrosine kinase (RTK)-initiated signaling networks upon activation by Pdgf-ββ, Fgf-2, or Igf-1 and identified more than 40,000 phosphorylation sites, including many phosphotyrosine sites without additional enrichment. The analysis revealed RTK-specific regulation of hundreds of pTyr sites on key signaling molecules. We found the tyrosine phosphatase Shp-2 to be the master regulator of Pdgfr pTyr signaling. Application of a recently introduced allosteric Shp-2 inhibitor revealed global regulation of the Pdgf-dependent tyrosine phosphoproteome, which significantly impaired cell migration. In addition, we present a list of hundreds of Shp-2-dependent targets and putative substrates, including Rasa1 and Cortactin with increased pTyr and Gab1 and Erk1/2 with decreased pTyr. Our study demonstrates that large-scale quantitative phosphoproteomics can precisely dissect tightly regulated kinase-phosphatase signaling networks.

AB - Despite its low cellular abundance, phosphotyrosine (pTyr) regulates numerous cell signaling pathways in health and disease. We applied comprehensive phosphoproteomics to unravel differential regulators of receptor tyrosine kinase (RTK)-initiated signaling networks upon activation by Pdgf-ββ, Fgf-2, or Igf-1 and identified more than 40,000 phosphorylation sites, including many phosphotyrosine sites without additional enrichment. The analysis revealed RTK-specific regulation of hundreds of pTyr sites on key signaling molecules. We found the tyrosine phosphatase Shp-2 to be the master regulator of Pdgfr pTyr signaling. Application of a recently introduced allosteric Shp-2 inhibitor revealed global regulation of the Pdgf-dependent tyrosine phosphoproteome, which significantly impaired cell migration. In addition, we present a list of hundreds of Shp-2-dependent targets and putative substrates, including Rasa1 and Cortactin with increased pTyr and Gab1 and Erk1/2 with decreased pTyr. Our study demonstrates that large-scale quantitative phosphoproteomics can precisely dissect tightly regulated kinase-phosphatase signaling networks.

KW - label-free quantitation

KW - mass spectrometry

KW - orbitrap

KW - PDGF

KW - phosphoproteomics

KW - Q exactive

KW - Shp-2

KW - SHP099

KW - TiO2

KW - tyrosine phosphorylation

U2 - 10.1016/j.celrep.2018.02.038

DO - 10.1016/j.celrep.2018.02.038

M3 - Journal article

C2 - 29514104

VL - 22

SP - 2784

EP - 2796

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 10

ER -

ID: 192400927