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Interdependence between EGFR and Phosphatases Spatially Established by Vesicular Dynamics Generates a Growth Factor Sensing and Responding Network

MPG-Autoren
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Stanoev,  Angel
Abt. II: Systemische Zellbiologie, Max Planck Institute of Molecular Physiology, Max Planck Society;

/persons/resource/persons221171

Mhamane,  Amit
Abt. II: Systemische Zellbiologie, Max Planck Institute of Molecular Physiology, Max Planck Society;

/persons/resource/persons118362

Schuermann,  Klaus Christian
Abt. II: Systemische Zellbiologie, Max Planck Institute of Molecular Physiology, Max Planck Society;

/persons/resource/persons98695

Grecco,  Hernán E.
Abt. II: Systemische Zellbiologie, Max Planck Institute of Molecular Physiology, Max Planck Society;

/persons/resource/persons224579

Stallaert,  Wayne
Abt. II: Systemische Zellbiologie, Max Planck Institute of Molecular Physiology, Max Planck Society;

/persons/resource/persons186225

Baumdick,  Martin
Abt. II: Systemische Zellbiologie, Max Planck Institute of Molecular Physiology, Max Planck Society;

/persons/resource/persons134902

Brüggemann,  Yannick
Abt. II: Systemische Zellbiologie, Max Planck Institute of Molecular Physiology, Max Planck Society;

/persons/resource/persons226506

Joshi,  Maitreyi S.
Abt. II: Systemische Zellbiologie, Max Planck Institute of Molecular Physiology, Max Planck Society;

/persons/resource/persons226510

Roda-Navarro,  Pedro
Abt. II: Systemische Zellbiologie, Max Planck Institute of Molecular Physiology, Max Planck Society;

/persons/resource/persons134298

Fengler,  Sven
Abt. II: Systemische Zellbiologie, Max Planck Institute of Molecular Physiology, Max Planck Society;

/persons/resource/persons181287

Stockert,  Rabea
Abt. II: Systemische Zellbiologie, Max Planck Institute of Molecular Physiology, Max Planck Society;

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Rossmannek,  Lisaweta
Abt. II: Systemische Zellbiologie, Max Planck Institute of Molecular Physiology, Max Planck Society;

/persons/resource/persons226508

Luig,  Jutta
Abt. II: Systemische Zellbiologie, Max Planck Institute of Molecular Physiology, Max Planck Society;

/persons/resource/persons118347

Koseska,  Aneta       
Abt. II: Systemische Zellbiologie, Max Planck Institute of Molecular Physiology, Max Planck Society;
Lise Meitner Group Cellular Computations and Learning, Center of Advanced European Studies and Research (caesar), Max Planck Society;

/persons/resource/persons98677

Bastiaens,  Philippe I. H.
Abt. II: Systemische Zellbiologie, Max Planck Institute of Molecular Physiology, Max Planck Society;

Externe Ressourcen

https://www.sciencedirect.com/science/article/pii/S2405471218302461
(Verlagsversion)

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Zitation

Stanoev, A., Mhamane, A., Schuermann, K. C., Grecco, H. E., Stallaert, W., Baumdick, M., et al. (2018). Interdependence between EGFR and Phosphatases Spatially Established by Vesicular Dynamics Generates a Growth Factor Sensing and Responding Network. Cell Systems, 7(3): e11, pp. 295-309. doi:10.1016/j.cels.2018.06.006.


Zitierlink: https://hdl.handle.net/21.11116/0000-000D-566E-8
Zusammenfassung
The proto-oncogenic epidermal growth factor receptor (EGFR) is a tyrosine kinase whose sensitivity to growth factors and signal duration determines cellular behavior. We resolve how EGFR's response to epidermal growth factor (EGF) originates from dynamically established recursive interactions with spatially organized protein tyrosine phosphatases (PTPs). Reciprocal genetic PTP perturbations enabled identification of receptor-like PTPRG/J at the plasma membrane and ER-associated PTPN2 as the major EGFR dephosphorylating activities. Imaging spatial-temporal PTP reactivity revealed that vesicular trafficking establishes a spatially distributed negative feedback with PTPN2 that determines signal duration. On the other hand, single-cell dose-response analysis uncovered a reactive oxygen species-mediated toggle switch between autocatalytically activated monomeric EGFR and the tumor suppressor PTPRG that governs EGFR's sensitivity to EGF. Vesicular recycling of monomeric EGFR unifies the interactions with these PTPs on distinct membrane systems, dynamically generating a network architecture that can sense and respond to time-varying growth factor signals.