ArticleThe Journal of biological chemistry2014
Regulation of Fc∈RI signaling in mast cells by G protein-coupled receptor kinase 2 and its RH domain.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Unveiling the Role of GRK2: From Immune Regulation to Cancer Therapeutics.Mediators of inflammation · 2025Review
- GRK2 differentially regulates FcεRI and MRGPRB2-mediated responses in mast cells.Frontiers in immunology · 2023Article
- Dynamin-related protein 1 differentially regulates FcεRI- and substance P-induced mast cell activation.The Journal of allergy and clinical immunology · 2022Article
- Novel inhibitors of phosphorylation independent activity of GRK2 modulate cAMP signaling.Pharmacology research & perspectives · 2022Article
- GRK2 inhibitors, paroxetine and CCG258747, attenuate IgE-mediated anaphylaxis but activate mast cellsFrontiers in immunology · 2022Article
- RGS proteins, GRKs, and beta-arrestins modulate G protein-mediated signaling pathways in asthma.Pharmacology & therapeutics · 2021Review
- Inhibition of Orai Channel Function Regulates Mas-Related G Protein-Coupled Receptor-Mediated Responses in Mast Cells.Frontiers in immunology · 2021Article
- G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases.Frontiers in immunology · 2021Review
- 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
- G protein-coupled receptor kinase 2 (GRK2) as a multifunctional signaling hub.Cellular and molecular life sciences : CMLS · 2019Review
- G Protein-Coupled Receptor Kinases in the Inflammatory Response and Signaling.Advances in immunology · 2017Review
- SNAP23-Dependent Surface Translocation of Leukotriene B4 (LTB4) Receptor 1 Is Essential for NOX2-Mediated Exocytotic Degranulation in Human Mast Cells Induced by Trichomonas vaginalis-Secreted LTB4.Infection and immunity · 2017Article
- Modulation of host defense peptide-mediated human mast cell activation by LPS.Innate immunity · 2016Article
- G-protein-coupled receptor kinases in inflammation and disease.Genes and immunity · 2015Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Agonist-induced phosphorylation of G protein-coupled receptors (GPCRs) by GPCRkinases (GRKs) promotes their desensitization and internalization. Here, we sought to determine the role of GRK2 on Fc∈RI signaling and mediator release in mast cells. The strategies utilized included lentiviral shRNA-mediated GRK2 knockdown, GRK2 gene deletion (GRK2(flox/flox)/cre recombinase) and overexpression of GRK2 and its regulator of G protein signaling homology (RH) domain (GRK2-RH). We found that silencing GRK2 expression caused ~50% decrease in antigen-induced Ca(2+) mobilization and degranulation but resulted in ablation of cytokine (IL-6 and IL-13) generation. The effect of GRK2 on cytokine generation does not require its catalytic activity but is mediated via the phosphorylation of p38 and Akt. Overexpression of GRK2 or its RH domain (GRK2-RH) enhanced antigen-induced mast cell degranulation and cytokine generation without affecting the expression levels of any of the Fc∈RI subunits (α, β, and γ). GRK2 or GRK2-RH had no effect on antigen-induced phosphorylation of Fc∈RIγ or Src but enhanced tyrosine phosphorylation of Syk. These data demonstrate that GRK2 modulates Fc∈RI signaling in mast cells via at least two mechanisms.One involves GRK2-RH and modulates tyrosine phosphorylation of Syk, and the other is mediated via the phosphorylation of p38 and Akt.
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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.