ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2019
Effects of ATP-competitive and function-selective ERK inhibitors on airway smooth muscle cell proliferation.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
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Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
- Mechanisms and therapeutic strategies of asthma: from bench to bedside.Signal transduction and targeted therapy · 2026Review
- Integrated airway epithelial signaling networks linking allergen-driven inflammation to airway remodeling in asthma.Frontiers in immunology · 2026Review
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- Proteomic Analysis to Identify Prospective Biomarkers of Treatment Outcome After Microvascular Decompression for Trigeminal Neuralgia: A Preliminary Study.The journal of pain · 2024Article
- Crosstalk between diacylglycerol kinase and protein kinase A in the regulation of airway smooth muscle cell proliferation.Respiratory research · 2023Article
- Selective Inhibition of Extracellular Signal-regulated Kinases 1 and 2: When Less Is More.American journal of respiratory cell and molecular biology · 2023Article
- Alterations in cytoskeletal and CaFrontiers in cardiovascular medicine · 2023Article
- Targeted Inhibition of Select Extracellular Signal-regulated Kinases 1 and 2 Functions Mitigates Pathological Features of Asthma in Mice.American journal of respiratory cell and molecular biology · 2023Article
- Regulation of Airway Smooth Muscle Cell Proliferation by Diacylglycerol Kinase: Relevance to Airway Remodeling in Asthma.International journal of molecular sciences · 2022Article
- Molecular determinants of airway smooth muscle cells in health and disease.Annals of translational medicine · 2022Article
- Targeting mitochondrial metabolism for metastatic cancer therapy.Molecular carcinogenesis · 2022Review
- Autocrine regulation of airway smooth muscle contraction by diacylglycerol kinase.Journal of cellular physiology · 2022Article
- Emerging Roles of Non-Coding RNAs in Childhood Asthma.Frontiers in pharmacology · 2022Review
- Dysregulated retinoic acid signaling in airway smooth muscle cells in asthma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
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- The Human Innate Immune Protein Calprotectin Elicits a Multimetal Starvation Response in Pseudomonas aeruginosa.Microbiology spectrum · 2021Article
- Multi-omic Analysis of Non-human Primate Heart after Partial-body Radiation with Minimal Bone Marrow Sparing.Health physics · 2021Article
- Mechanistic Analysis of an Extracellular Signal-Regulated Kinase 2-Interacting Compound that Inhibits Mutant BRAF-Expressing Melanoma Cells by Inducing Oxidative Stress.The Journal of pharmacology and experimental therapeutics · 2021Article
- Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Increased airway smooth muscle (ASM) cell mass and secretory functions are characteristics of airway inflammatory diseases, such as asthma. To date, there are no effective therapies to combat ASM cell proliferation, which contributes to bronchoconstriction and airway obstruction. Growth factors such as platelet-derived growth factor (PDGF) and the activation of the ERK1/2 are major regulators of ASM cell proliferation and airway remodeling in asthma. However, given the ubiquitous expression and multiple functions of ERK1/2, complete inhibition of ERK1/2 using ATP-competitive inhibitors may lead to unwanted off-target effects. Alternatively, we have identified compounds that are designed to target substrate docking sites and act as function-selective inhibitors of ERK1/2 signaling. Here, we show that both function-selective and ATP-competitive ERK1/2 inhibitors are effective at inhibiting PDGF-mediated proliferation, collagen production, and IL-6 secretion in ASM cells. Proteomic analysis revealed that both types of inhibitors had similar effects on reducing proteins related to TGF-β and IL-6 signaling that are relevant to airway remodeling. However, function-selective ERK1/2 inhibitors caused fewer changes in protein expression compared with ATP-competitive inhibitors. These studies provide a molecular basis for the development of function-selective ERK1/2 inhibitors to mitigate airway remodeling in asthma with defined regulation of ERK1/2 signaling.-Defnet, A. E., Huang, W., Polischak, S., Yadav, S. K., Kane, M. A., Shapiro, P., Deshpande, D. A. Effects of ATP-competitive and function-selective ERK inhibitors on airway smooth muscle cell proliferation.
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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.