ArticleCell systems2017
Linear Integration of ERK Activity Predominates over Persistence Detection in Fra-1 Regulation.
Article in Cell systems, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed.
- Rapid transcriptional response to a dynamic morphogen by time integration.Current biology : CB · 2026Article
- Single-cell morphodynamical trajectories enable prediction of gene expression accompanying cell state change.Cell systems · 2026Article
- Genetic Anatomy and Ontogenetic Roles of Early Growth Response 1 (Egr1) in Human and Mouse.Development & reproduction · 2026Review
- Transient proliferation by reversible YAP and mitogen control of the cyclin D1/p27 ratio.Communications biology · 2026Article
- Serial Imaging of Tumour and microEnvironment (SITE) platform for live-cellbioRxiv : the preprint server for biology · 2025Article
- Deciphering the history of ERK activity from fixed-cell immunofluorescence measurements.Nature communications · 2025Article
- Dynamical and combinatorial coding by MAPK p38 and NFκB in the inflammatory response of macrophages.Molecular systems biology · 2024Article
- Mitogen signaling strength and duration can control cell cycle decisions.Science advances · 2024Review
- Dietary restriction modulates ultradian rhythms and autocorrelation properties in mice behavior.Communications biology · 2024Article
- Time-integrated BMP signaling determines fate in a stem cell model for early human development.Nature communications · 2024Article
- Host-derived growth factors drive ERK phosphorylation and MCL1 expression to promote osteosarcoma cell survival during metastatic lung colonization.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Re-expression of epigenetically silenced PTPRR by histone acetylation sensitizes RAS-mutant lung adenocarcinoma to SHP2 inhibition.Cellular and molecular life sciences : CMLS · 2024Article
- Review
- A guide to ERK dynamics, part 1: mechanisms and models.The Biochemical journal · 2023Article
- A guide to ERK dynamics, part 2: downstream decoding.The Biochemical journal · 2023Article
- Automatic detection of spatio-temporal signaling patterns in cell collectives.The Journal of cell biology · 2023Article
- Overexpression of FRA1 (Cells · 2023Article
- Article
- Dynamics of an incoherent feedforward loop drive ERK-dependent pattern formation in the early Drosophila embryo.Development (Cambridge, England) · 2023Article
- Multiple cancers escape from multiple MAPK pathway inhibitors and use DNA replication stress signaling to tolerate aberrant cell cycles.Science signaling · 2023Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors.
Funding
Abstract
ERK signaling regulates the expression of target genes, but it is unclear how ERK activity dynamics are interpreted. Here, we investigate this question using simultaneous, live, single-cell imaging of two ERK activity reporters and expression of Fra-1, a target gene controlling epithelial cell identity. We find that Fra-1 is expressed in proportion to the amplitude and duration of ERK activity. In contrast to previous "persistence detector" and "selective filter" models in which Fra-1 expression only occurs when ERK activity persists beyond a threshold duration, our observations demonstrate that the network regulating Fra-1 expression integrates total ERK activity and responds to it linearly. However, exploration of a generalized mathematical model of the Fra-1 coherent feedforward loop demonstrates that it can perform either linear integration or persistence detection, depending on the basal mRNA production rate and protein production delays. Our data indicate that significant basal expression and short delays cause Fra-1 to respond linearly to integrated ERK activity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.