ArticleMolecular systems biology2014
Data-driven modeling reconciles kinetics of ERK phosphorylation, localization, and activity states.
Article in Molecular systems biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 53 citations in OpenAlex.
- A single mechanism can explain network-wide insulin resistance in adipocytes from obese patients with type 2 diabetes.The Journal of biological chemistry · 2014Trial
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- A naturally synonymous mutation modulates an ERK-centered regulatory network to mediate thermotolerance divergence in Crassostrea oysters.Communications biology · 2026Article
- Reconstructing and comparing signal transduction networks from single-cell protein quantification data.Bioinformatics (Oxford, England) · 2026Article
- Two novel red-FRET ERK bosensors in the 670-720 nm range.Journal of biological engineering · 2025Article
- Matrix Stiffness and Biochemistry Govern Colorectal Cancer Cell Growth and Signaling in User-Programmable Synthetic Hydrogels.ACS biomaterials science & engineering · 2025Article
- A guide to ERK dynamics, part 1: mechanisms and models.The Biochemical journal · 2023Article
- On the inference of ERK signaling dynamics from protein biosensor measurements.Molecular biology of the cell · 2023Article
- Subcellular partitioning of protein kinase activity revealed by functional kinome profiling.Scientific reports · 2022Article
- Signaling Pathways in Proton and Non-proton ASIC1a Activation.Frontiers in cellular neuroscience · 2021Article
- Optical control of MAP kinase kinase 6 (MKK6) reveals that it has divergent roles in pro-apoptotic and anti-proliferative signaling.The Journal of biological chemistry · 2020Article
- Hexokinase 2 Promotes Cell Growth and Tumor Formation Through the Raf/MEK/ERK Signaling Pathway in Cervical Cancer.Frontiers in oncology · 2020Article
- Optical control of protein phosphatase function.Nature communications · 2019Article
- Genetically Encoded Fluorescent Biosensors Illuminate the Spatiotemporal Regulation of Signaling Networks.Chemical reviews · 2018Review
- Importance of Feedback and Feedforward Loops to Adaptive Immune Response Modeling.CPT: pharmacometrics & systems pharmacology · 2018Review
- Signaling pathways as linear transmitters.eLife · 2018Article
- Identification of PTPN1 as a novel negative regulator of the JNK MAPK pathway using a synthetic screening for pathway-specific phosphatases.Scientific reports · 2017Article
- Two faces of competition: target-mediated reverse signalling in microRNA and mitogen-activated protein kinase regulatory networks.IET systems biology · 2017Review
- Kinetic Modeling and Analysis of the Akt/Mechanistic Target of Rapamycin Complex 1 (mTORC1) Signaling Axis Reveals Cooperative, Feedforward Regulation.The Journal of biological chemistry · 2017Article
- Sampling-based Bayesian approaches reveal the importance of quasi-bistable behavior in cellular decision processes on the example of the MAPK signaling pathway in PC-12 cell lines.BMC systems biology · 2017Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The extracellular signal-regulated kinase (ERK) signaling pathway controls cell proliferation and differentiation in metazoans. Two hallmarks of its dynamics are adaptation of ERK phosphorylation, which has been linked to negative feedback, and nucleocytoplasmic shuttling, which allows active ERK to phosphorylate protein substrates in the nucleus and cytosol. To integrate these complex features, we acquired quantitative biochemical and live-cell microscopy data to reconcile phosphorylation, localization, and activity states of ERK. While maximal growth factor stimulation elicits transient ERK phosphorylation and nuclear translocation responses, ERK activities available to phosphorylate substrates in the cytosol and nuclei show relatively little or no adaptation. Free ERK activity in the nucleus temporally lags the peak in nuclear translocation, indicating a slow process. Additional experiments, guided by kinetic modeling, show that this process is consistent with ERK's modification of and release from nuclear substrate anchors. Thus, adaptation of whole-cell ERK phosphorylation is a by-product of transient protection from phosphatases. Consistent with this interpretation, predictions concerning the dose-dependence of the pathway response and its interruption by inhibition of MEK were experimentally confirmed.
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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.