ArticleMolecular systems biology2020
Oncogenic mutant RAS signaling activity is rescaled by the ERK/MAPK pathway.
Article in Molecular systems biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 58 citations in OpenAlex.
- A Far-Red FRET biosensor for AMPK enables multiplexed imaging of single-cell bioenergetic homeostasis.bioRxiv : the preprint server for biology · 2026Article
- Oncogene-Mechanics Axis: KRAS G12C Confers Agility Enabling Malignant Mechano-responses to Peristalsis in Colorectal Cancer.bioRxiv : the preprint server for biology · 2026Article
- Are physiological oscillations physiological?The Journal of physiology · 2026Review
- Constitutively active RAS prolongs Cdc42 signalling, while MAPK signalling is attenuated during fission yeast mating.PLoS genetics · 2026Article
- Positive cooperativity between RAS-binding and cysteine-rich domains regulates RAF membrane binding kinetics via lateral rebinding.Nature communications · 2026Article
- Systems-level consequences of low RAF abundance for EGFR-ERK signaling.Biophysical journal · 2026Article
- Robust calibration and quantification of FRET signals using multiplexed biosensor barcoding.iScience · 2025Article
- Mechanism of ERK-mediated Rho Activation and Stress Fiber Assembly for Cell Migration.bioRxiv : the preprint server for biology · 2025Article
- Two novel red-FRET ERK bosensors in the 670-720 nm range.Journal of biological engineering · 2025Article
- Erk1Oncogene · 2025Article
- Deciphering the history of ERK activity from fixed-cell immunofluorescence measurements.Nature communications · 2025Article
- First molecules to reactivate RASBMC cancer · 2025Article
- CDK2 activity crosstalk on the ERK kinase translocation reporter can be resolved computationally.Cell systems · 2025Article
- Gene-knockdown Methods for Silencing Nuclear-localized Insulin Receptors in Lung Adenocarcinoma Cells: A Bioinformatics Approach.Current genomics · 2025Article
- The role of neuroendocrine differentiation in treatment resistance of prostate cancer and intervention strategies.Frontiers in oncology · 2025Review
- Monitoring Cellular Energy Balance in Single Cells Using Fluorescent Biosensors for AMPK.Methods in molecular biology (Clifton, N.J.) · 2025Article
- pERK transition-induced directional mode switching promotes epithelial tumor cell migration.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- D3S-001, a KRAS G12C Inhibitor with Rapid Target Engagement Kinetics, Overcomes Nucleotide Cycling, and Demonstrates Robust Preclinical and Clinical Activities.Cancer discovery · 2024Article
- Systems modeling of oncogenic G-protein and GPCR signaling reveals unexpected differences in downstream pathway activation.NPJ systems biology and applications · 2024Article
- Signal execution modes emerge in biochemical reaction networks calibrated to experimental data.iScience · 2024Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Activating mutations in RAS are present in ~ 30% of human tumors, and the resulting aberrations in ERK/MAPK signaling play a central role in oncogenesis. However, the form of these signaling changes is uncertain, with activating RAS mutants linked to both increased and decreased ERK activation in vivo. Rationally targeting the kinase activity of this pathway requires clarification of the quantitative effects of RAS mutations. Here, we use live-cell imaging in cells expressing only one RAS isoform to quantify ERK activity with a new level of accuracy. We find that despite large differences in their biochemical activity, mutant KRAS isoforms within cells have similar ranges of ERK output. We identify roles for pathway-level effects, including variation in feedback strength and feedforward modulation of phosphatase activity, that act to rescale pathway sensitivity, ultimately resisting changes in the dynamic range of ERK activity while preserving responsiveness to growth factor stimuli. Our results reconcile seemingly inconsistent reports within the literature and imply that the signaling changes induced by RAS mutations early in oncogenesis are subtle.
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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.