ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014
Exploiting functional domains of GRK2/3 to alter the competitive balance of pro- and anticontractile signaling in airway smooth muscle.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Rhinovirus C15 Attenuates Relaxation and cAMP Production in Human Airways and Smooth Muscle.American journal of respiratory cell and molecular biology · 2023Article
- In silico identification of a βProceedings of the National Academy of Sciences of the United States of America · 2022Article
- PD 102807 Induces M3 mAChR-Dependent GRK-/Arrestin-Biased Signaling in Airway Smooth Muscle Cells.American journal of respiratory cell and molecular biology · 2022Article
- Airway smooth muscle and airway hyperresponsiveness in asthma: mechanisms of airway smooth muscle dysfunction.Minerva medica · 2022Article
- Diacylglycerol Kinase Inhibition Reduces Airway Contraction by Negative Feedback Regulation of Gq-Signaling.American journal of respiratory cell and molecular biology · 2021Article
- G Protein-Coupled Receptor Kinase 2 (GRK2) Regulates T Cell Response in a Murine Model of House Dust Mite-Induced Asthma.Frontiers in allergy · 2021Article
- Dexamethasone rescues TGF-β1-mediated βRespiratory research · 2020Article
- Regulation of ovarian cancer G protein-coupled receptor-1 expression and signaling.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Endogenous c-Jun N-terminal kinase (JNK) activity marks the boundary between normal and malignant granulosa cells.Cell death & disease · 2018Article
- GαBritish journal of pharmacology · 2017Article
- Ixazomib enhances parathyroid hormone-induced β-catenin/T-cell factor signaling by dissociating β-catenin from the parathyroid hormone receptor.Molecular biology of the cell · 2017Article
- βHandbook of experimental pharmacology · 2017Review
- Antimitogenic effect of bitter taste receptor agonists on airway smooth muscle cells.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- Specificity of arrestin subtypes in regulating airway smooth muscle G protein-coupled receptor signaling and function.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
- Disruption of β-catenin binding to parathyroid hormone (PTH) receptor inhibits PTH-stimulated ERK1/2 activation.Biochemical and biophysical research communications · 2015Article
- Mapping functional group free energy patterns at protein occluded sites: nuclear receptors and G-protein coupled receptors.Journal of chemical information and modeling · 2015Article
- Crosstalk between beta-2-adrenoceptor and muscarinic acetylcholine receptors in the airway.Current opinion in pharmacology · 2014Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
To clarify the potential utility of targeting GRK2/3-mediated desensitization as a means of manipulating airway smooth muscle (ASM) contractile state, we assessed the specificity of GRK2/3 regulation of procontractile and relaxant G-protein-coupled receptors in ASM. Functional domains of GRK2/3 were stably expressed, or siRNA-mediated GRK2/3 knockdown was performed, in human ASM cultures, and agonist-induced signaling was assessed. Regulation of contraction of murine tracheal rings expressing GRK2 C terminus was also assessed. GRK2/3 knockdown or expression of the GRK2 C terminus caused a significant (∼ 30-90%) increase in maximal β-agonist and histamine [phosphoinositide (PI) hydrolysis] signaling, without affecting the calculated EC50. GRK2 C-terminal expression did not affect signaling by methacholine, thrombin, or LTD4. Expression of the GRK2 N terminus or kinase-dead holo-GRK2 diminished (∼ 30-70%) both PI hydrolysis and Ca(2+) mobilization by every Gq-coupled receptor examined. Under conditions of GRK2 C-terminal expression, β-agonist inhibition of methacholine-stimulated PI hydrolysis was greater. Finally, transgenic expression of the GRK2 C terminus in murine ASM enabled ∼ 30-50% greater β-agonist-mediated relaxation of methacholine-induced contraction. Collectively these data demonstrate the relative selectivity of GRKs for the β2AR in ASM and the ability to exploit GRK2/3 functional domains to render ASM hyporesponsive to contractile agents while increasing responsiveness to bronchodilating β-agonist.
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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.