ArticleScience signaling2020
Kinetics of receptor tyrosine kinase activation define ERK signaling dynamics.
Article in Science signaling, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
42 citing papers in PubMed, 93 citations in OpenAlex.
- Vitronectin Enrichment in Prostate Cancer Liver Metastases Promotes Adhesion and Survival.Cancer research communications · 2026Article
- Glioma-intrinsic MAPK/ERK signaling promotes immunotherapy efficacy through T cell infiltration and interferon responses.Nature communications · 2026Article
- Integrative multi-omics defines melanoma drug response networks and ARID1A-dependent resistance mechanisms.Molecular systems biology · 2026Article
- The role of kinase domain dimerization in EGFR activation.Structure (London, England : 1993) · 2026Article
- Temporal photoproximity labeling of ligand-activated EGFR neighborhoods using MultiMap.Nature chemical biology · 2026Article
- Dynamic control of Raf-ERK signaling modulates neuronal activity across biological scales.bioRxiv : the preprint server for biology · 2026Article
- Single-Molecule FRET-Tracking of InlB-Activated MET Receptors in Living Cells.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Phlorotannins fromMarine drugs · 2025Article
- Dysregulated Resolution of Inflammation After Respiratory Viral Infections: Molecular Pathways Linking Neuroinflammation to Post-Viral Neuropathic Pain-A Narrative Review.International journal of molecular sciences · 2025Review
- Article
- Article
- Uptake Inhibition to Improve Bioavailability of Nanoparticle-Mediated Growth Factor Delivery to the Corneal Epithelium.ACS pharmacology & translational science · 2025Article
- Matrix Stiffness and Biochemistry Govern Colorectal Cancer Cell Growth and Signaling in User-Programmable Synthetic Hydrogels.ACS biomaterials science & engineering · 2025Article
- Overexpression of Nogo-A changes nerve growth factor signaling dynamics in PC12 cells.Cellular signalling · 2025Article
- Article
- SPROUTY2, a Negative Feedback Regulator of Receptor Tyrosine Kinase Signaling, Associated with Neurodevelopmental Disorders: Current Knowledge and Future Perspectives.International journal of molecular sciences · 2024Review
- Mathematical Modeling and Inference of Epidermal Growth Factor-Induced Mitogen-Activated Protein Kinase Cell Signaling Pathways.International journal of molecular sciences · 2024Review
- MAPK/ERK signaling in gliomas modulates interferon responses, T cell recruitment, microglia phenotype, and immune checkpoint blockade efficacy.bioRxiv : the preprint server for biology · 2024Article
- Mitogen signaling strength and duration can control cell cycle decisions.Science advances · 2024Review
- Minocycline Inhibits Tick-Borne Encephalitis Virus and Protects Infected Cells via Multiple Pathways.Viruses · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
In responses to activation of receptor tyrosine kinases (RTKs), crucial cell fate decisions depend on the duration and dynamics of ERK signaling. In PC12 cells, epidermal growth factor (EGF) induces transient ERK activation that leads to cell proliferation, whereas nerve growth factor (NGF) promotes sustained ERK activation and cell differentiation. These differences have typically been assumed to reflect distinct feedback mechanisms in the Raf-MEK-ERK signaling network, with the receptors themselves acting as simple upstream inputs. We failed to confirm the expected differences in feedback type when investigating transient versus sustained signaling downstream of the EGF receptor (EGFR) and NGF receptor (TrkA). Instead, we found that ERK signaling faithfully followed RTK dynamics when receptor signaling was modulated in different ways. EGFR activation kinetics, and consequently ERK signaling dynamics, were switched from transient to sustained when receptor internalization was inhibited with drugs or mutations, or when cells expressed a chimeric receptor likely to have impaired dimerization. In addition, EGFR and ERK signaling both became more sustained when substoichiometric levels of erlotinib were added to reduce duration of EGFR kinase activation. Our results argue that RTK activation kinetics play a crucial role in determining MAP kinase cascade signaling dynamics and cell fate decisions, and that signaling outcome can be modified by activating a given RTK in different ways.
Indexed as
Identifiers
What OpenQuestion holds
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.