ArticleMolecular bioSystems2010
Structure of the EGF receptor transactivation circuit integrates multiple signals with cell context.
Article in Molecular bioSystems, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Frequency-Dependent Premature Differentiation of Pheochromocytoma Cells Exhibits Band-Pass Filter Behavior Correlation with Intracellular Enzyme Activation Kinetics.International journal of molecular sciences · 2025Article
- The network response to Egf is tissue-specific.iScience · 2025Article
- A Frequency Domain Analysis of the Growth Factor-Driven Extra-Cellular-Regulated Kinase (ERK) Pathway.Biology · 2025Article
- Cellular context alters EGF-induced ERK dynamics and reveals potential crosstalk with GDF-15.Biomicrofluidics · 2022Article
- Dynamics and Sensitivity of Signaling Pathways.Current pathobiology reports · 2022Article
- A Live-Cell Screen for Altered Erk Dynamics Reveals Principles of Proliferative Control.Cell systems · 2020Article
- A systems perspective of heterocellular signaling.Essays in biochemistry · 2018Review
- Composite regulation of ERK activity dynamics underlying tumour-specific traits in the intestine.Nature communications · 2018Article
- EGFR signaling pathways are wired differently in normal 184A1L5 human mammary epithelial and MDA-MB-231 breast cancer cells.Journal of cell communication and signaling · 2017Article
- Conservation of protein abundance patterns reveals the regulatory architecture of the EGFR-MAPK pathway.Science signaling · 2016Article
- Targeting autocrine HB-EGF signaling with specific ADAM12 inhibition using recombinant ADAM12 prodomain.Scientific reports · 2015Article
- Open questions: the disrupted circuitry of the cancer cell.BMC biology · 2014Article
- Autocrine HBEGF expression promotes breast cancer intravasation, metastasis and macrophage-independent invasion in vivo.Oncogene · 2014Article
- Article
- Data-driven modeling reconciles kinetics of ERK phosphorylation, localization, and activity states.Molecular systems biology · 2014Article
- ADAM-10 and -17 regulate endometriotic cell migration via concerted ligand and receptor shedding feedback on kinase signaling.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Models of signalling networks - what cell biologists can gain from them and give to them.Journal of cell science · 2013Review
- Single-cell and subcellular pharmacokinetic imaging allows insight into drug action in vivo.Nature communications · 2013Article
- Exocrine pancreatic carcinogenesis and autotaxin expression.PloS one · 2012Article
- Biology using engineering tools: the negative feedback amplifier.Cell cycle (Georgetown, Tex.) · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Transactivation of the epidermal growth factor receptor (EGFR) is thought to be a process by which a variety of cellular inputs can be integrated into a single signaling pathway through either stimulated proteolysis (shedding) of membrane-anchored EGFR ligands or by modification of the activity of the EGFR. As a first step towards building a predictive model of the EGFR transactivation circuit, we quantitatively defined how signals from multiple agonists were integrated both upstream and downstream of the EGFR to regulate extracellular signal regulated kinase (ERK) activity in human mammary epithelial cells. By using a "non-binding" reporter of ligand shedding, we found that transactivation triggers a positive feedback loop from ERK back to the EGFR such that ligand shedding drives EGFR-stimulated ERK that in turn drives further ligand shedding. Importantly, activated Ras and ERK levels were nearly linear functions of ligand shedding and the effect of multiple, sub-saturating inputs was additive. Simulations showed that ERK-mediated feedback through ligand shedding resulted in a stable steady-state level of activated ERK, but also showed that the extracellular environment can modulate the level of feedback. Our results suggest that the transactivation circuit acts as a context-dependent integrator and amplifier of multiple extracellular signals and that signal integration can effectively occur at multiple points in the EGFR pathway.
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Registered trials
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 OpenQuestion graph.