ArticlePloS one2011
Regulation of C3a receptor signaling in human mast cells by G protein coupled receptor kinases.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 59 citations in OpenAlex.
- Molecular basis of diverse ligand recognition and species-specific pharmacology at the complement anaphylatoxin receptor C3aR.Nature communications · 2026Article
- Subnanomolar MAS-related G protein-coupled receptor-X2/B2 antagonists with efficacy in human mast cells and disease models.Signal transduction and targeted therapy · 2025Article
- Fibroblast derived C3 promotes the progression of experimental periodontitis through macrophage M1 polarization and osteoclast differentiation.International journal of oral science · 2025Article
- The complement system in human pregnancy and preeclampsia.Frontiers in immunology · 2025Review
- Transactivation of the EGF receptor as a novel desensitization mechanism for G protein-coupled receptors, illustrated by dopamine D2-like and βCellular & molecular biology letters · 2024Article
- Complement C3aR signaling: Immune and metabolic modulation and its impact on Alzheimer's disease.European journal of immunology · 2024Review
- Complement C3-Deficiency-Induced Constipation in FVB/N-C3International journal of molecular sciences · 2023Article
- Molecular basis of anaphylatoxin binding, activation, and signaling bias at complement receptors.Cell · 2023Article
- Mast Cells and Basophils in IgE-Independent Anaphylaxis.International journal of molecular sciences · 2023Review
- Structural biology of complement receptors.Frontiers in immunology · 2023Review
- 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
- Inhibition of MRGPRX2 but not FcεRI or MrgprB2-mediated mast cell degranulation by a small molecule inverse receptor agonist.Frontiers in immunology · 2022Article
- RGS proteins, GRKs, and beta-arrestins modulate G protein-mediated signaling pathways in asthma.Pharmacology & therapeutics · 2021Review
- Two Sides of the Coin: Mast Cells as a Key Regulator of Allergy and Acute/Chronic Inflammation.Cells · 2021Review
- A Critical Role for NaJournal of immunology (Baltimore, Md. : 1950) · 2021Article
- Mitochondrial C3a Receptor Activation in Oxidatively Stressed Epithelial Cells Reduces Mitochondrial Respiration and Metabolism.Frontiers in immunology · 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
- Interleukin-33 Amplifies Human Mast Cell Activities Induced by Complement Anaphylatoxins.Frontiers in immunology · 2020Article
- Identification of Gain and Loss of Function Missense Variants in MRGPRX2's Transmembrane and Intracellular Domains for Mast Cell Activation by Substance P.International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe complement component C3a activates human mast cells via its cell surface G protein coupled receptor (GPCR) C3aR. For most GPCRs, agonist-induced receptor phosphorylation leads to receptor desensitization, internalization as well as activation of downstream signaling pathways such as ERK1/2 phosphorylation. Previous studies in transfected COS cells overexpressing G protein coupled receptor kinases (GRKs) demonstrated that GRK2, GRK3, GRK5 and GRK6 participate in agonist-induced C3aR phosphorylation. However, the roles of these GRKs on the regulation of C3aR signaling and mediator release in human mast cells remain unknown. METHODOLOGY/PRINCIPAL
findingsWe utilized lentivirus short hairpin (sh)RNA to stably knockdown the expression of GRK2, GRK3, GRK5 and GRK6 in human mast cell lines, HMC-1 and LAD2, that endogenously express C3aR. Silencing GRK2 or GRK3 expression caused a more sustained Ca(2+) mobilization, attenuated C3aR desensitization, and enhanced degranulation as well as ERK1/2 phosphorylation when compared to shRNA control cells. By contrast, GRK5 or GRK6 knockdown had no effect on C3aR desensitization, but caused a significant decrease in C3a-induced mast cell degranulation. Interestingly, GRK5 or GRK6 knockdown rendered mast cells more responsive to C3a for ERK1/2 phosphorylation. CONCLUSION/SIGNIFICANCE: This study demonstrates that GRK2 and GRK3 are involved in C3aR desensitization. Furthermore, it reveals the novel finding that GRK5 and GRK6 promote C3a-induced mast cell degranulation but inhibit ERK1/2 phosphorylation via C3aR desensitization-independent mechanisms. These findings thus reveal a new level of complexity for C3aR regulation by GRKs in human mast cells.
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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.