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@ARTICLE{Stanoev:140235,
author = {Stanoev, Angel and Mhamane, Amit and Schuermann, Klaus C
and Grecco, Hernán E and Stallaert, Wayne and Baumdick,
Martin and Brüggemann, Yannick and Joshi, Maitreyi S and
Roda-Navarro, Pedro and Fengler, Sven and Stockert, Rabea
and Roßmannek, Lisaweta and Luig, Jutta and Koseska, Aneta
and Bastiaens, Philippe I H},
title = {{I}nterdependence between {EGFR} and {P}hosphatases
{S}patially {E}stablished by {V}esicular {D}ynamics
{G}enerates a {G}rowth {F}actor {S}ensing and {R}esponding
{N}etwork.},
journal = {Cell systems},
volume = {7},
number = {3},
issn = {2405-4712},
address = {Maryland Heights, MO},
publisher = {Elsevier},
reportid = {DZNE-2020-06557},
pages = {295-309.e11},
year = {2018},
abstract = {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.},
keywords = {Cell Membrane: metabolism / Computational Biology /
Cytoplasmic Vesicles: metabolism / Endoplasmic Reticulum:
metabolism / Epidermal Growth Factor: metabolism / ErbB
Receptors: metabolism / Feedback, Physiological / Humans /
MCF-7 Cells / Microscopy, Confocal / Models, Theoretical /
Phosphorylation / Protein Interaction Maps / Protein
Transport / Protein Tyrosine Phosphatase, Non-Receptor Type
2: metabolism / RNA, Small Interfering: genetics / Reactive
Oxygen Species: metabolism / Receptor-Like Protein Tyrosine
Phosphatases, Class 5: genetics / Receptor-Like Protein
Tyrosine Phosphatases, Class 5: metabolism / Signal
Transduction / Single-Cell Analysis / RNA, Small Interfering
(NLM Chemicals) / Reactive Oxygen Species (NLM Chemicals) /
Epidermal Growth Factor (NLM Chemicals) / EGFR protein,
human (NLM Chemicals) / ErbB Receptors (NLM Chemicals) /
PTPN2 protein, human (NLM Chemicals) / Protein Tyrosine
Phosphatase, Non-Receptor Type 2 (NLM Chemicals) /
Receptor-Like Protein Tyrosine Phosphatases, Class 5 (NLM
Chemicals)},
cin = {AG Fava 1},
ddc = {570},
cid = {I:(DE-2719)1013016},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30145116},
pmc = {pmc:PMC6167251},
doi = {10.1016/j.cels.2018.06.006},
url = {https://pub.dzne.de/record/140235},
}