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Disentangling Pro-mitotic Signaling during Cell Cycle Progression using Time-Resolved Single-Cell Imaging.

Benary, Manuela and Bohn, Stefan and Lüthen, Mareen and Nolis, Ilias K. and Blüthgen, Nils and Loewer, Alexander (2020):
Disentangling Pro-mitotic Signaling during Cell Cycle Progression using Time-Resolved Single-Cell Imaging.
In: Cell reports, 31 (2), p. 107514. ISSN 2211-1247,
DOI: 10.1016/j.celrep.2020.03.078,
[Article]

Abstract

Cells rely on input from extracellular growth factors to control their proliferation during development and adult homeostasis. Such mitogenic inputs are transmitted through multiple signaling pathways that synergize to precisely regulate cell cycle entry and progression. Although the architecture of these signaling networks has been characterized in molecular detail, their relative contribution, especially at later cell cycle stages, remains largely unexplored. By combining quantitative time-resolved measurements of fluorescent reporters in untransformed human cells with targeted pharmacological inhibitors and statistical analysis, we quantify epidermal growth factor (EGF)-induced signal processing in individual cells over time and dissect the dynamic contribution of downstream pathways. We define signaling features that encode information about extracellular ligand concentrations and critical time windows for inducing cell cycle transitions. We show that both extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K) activity are necessary for initial cell cycle entry, whereas only PI3K affects the duration of S phase at later stages of mitogenic signaling.

Item Type: Article
Erschienen: 2020
Creators: Benary, Manuela and Bohn, Stefan and Lüthen, Mareen and Nolis, Ilias K. and Blüthgen, Nils and Loewer, Alexander
Title: Disentangling Pro-mitotic Signaling during Cell Cycle Progression using Time-Resolved Single-Cell Imaging.
Language: English
Abstract:

Cells rely on input from extracellular growth factors to control their proliferation during development and adult homeostasis. Such mitogenic inputs are transmitted through multiple signaling pathways that synergize to precisely regulate cell cycle entry and progression. Although the architecture of these signaling networks has been characterized in molecular detail, their relative contribution, especially at later cell cycle stages, remains largely unexplored. By combining quantitative time-resolved measurements of fluorescent reporters in untransformed human cells with targeted pharmacological inhibitors and statistical analysis, we quantify epidermal growth factor (EGF)-induced signal processing in individual cells over time and dissect the dynamic contribution of downstream pathways. We define signaling features that encode information about extracellular ligand concentrations and critical time windows for inducing cell cycle transitions. We show that both extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K) activity are necessary for initial cell cycle entry, whereas only PI3K affects the duration of S phase at later stages of mitogenic signaling.

Journal or Publication Title: Cell reports
Journal volume: 31
Number: 2
Divisions: 10 Department of Biology
10 Department of Biology > Systems Biology of the Stress Response
Date Deposited: 20 Apr 2020 11:32
DOI: 10.1016/j.celrep.2020.03.078
Identification Number: pmid:32294432
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