Benary, Manuela ; Bohn, Stefan ; Lüthen, Mareen ; Nolis, Ilias K. ; Blüthgen, Nils ; Loewer, Alexander (2020)
Disentangling Pro-mitotic Signaling during Cell Cycle Progression using Time-Resolved Single-Cell Imaging.
In: Cell reports, 31 (2)
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 ; Bohn, Stefan ; Lüthen, Mareen ; Nolis, Ilias K. ; Blüthgen, Nils ; Loewer, Alexander |
| Type of entry: | Bibliographie |
| Title: | Disentangling Pro-mitotic Signaling during Cell Cycle Progression using Time-Resolved Single-Cell Imaging. |
| Language: | English |
| Date: | 14 April 2020 |
| Journal or Publication Title: | Cell reports |
| Volume of the journal: | 31 |
| Issue Number: | 2 |
| DOI: | 10.1016/j.celrep.2020.03.078 |
| 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. |
| Identification Number: | pmid:32294432 |
| Divisions: | 10 Department of Biology 10 Department of Biology > Systems Biology of the Stress Response |
| Date Deposited: | 20 Apr 2020 11:32 |
| Last Modified: | 20 Apr 2020 11:32 |
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