ArticleJournal of immunology (Baltimore, Md. : 1950)2014
G Protein-coupled receptor kinase-6 interacts with activator of G protein signaling-3 to regulate CXCR2-mediated cellular functions.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 25 citations in OpenAlex.
- A pilot study on reparixin, a CXCR1/2 antagonist, to assess safety and efficacy in attenuating ischaemia-reperfusion injury and inflammation after on-pump coronary artery bypass graft surgery.Clinical and experimental immunology · 2015Trial
- Soluble E-cadherin-CXCL1-CXCR2 axis as a therapeutic vulnerability in inflammatory breast cancer brain metastasis.Neuro-oncology · 2026Article
- Disruption of GPSM1/CSF1 signaling reprograms tumor-associated macrophages to overcome anti-PD-1 resistance in colorectal cancer.Journal for immunotherapy of cancer · 2025Article
- GPSM1 impairs metabolic homeostasis by controlling a pro-inflammatory pathway in macrophages.Nature communications · 2022Article
- CXCR2 Receptor: Regulation of Expression, Signal Transduction, and Involvement in Cancer.International journal of molecular sciences · 2022Review
- Review
- The PDZ motif peptide of ZO-1 attenuates Pseudomonas aeruginosa LPS-induced airway inflammation.Scientific reports · 2020Article
- Intersection of two key signal integrators in the cell: activator of G-protein signaling 3 and dishevelled-2.Journal of cell science · 2020Article
- Activator of G protein signaling 3 modulates prostate tumor development and progression.Carcinogenesis · 2019Article
- Mammalian diaphanous-related formin 1 (mDia1) coordinates mast cell migration and secretion through its actin-nucleating activity.The Journal of allergy and clinical immunology · 2019Article
- How do chemokines navigate neutrophils to the target site: Dissecting the structural mechanisms and signaling pathways.Cellular signalling · 2019Review
- Role of G-proteins and phosphorylation in the distribution of AGS3 to cell puncta.Journal of cell science · 2018Article
- Protein engineering of the chemokine CCL20 prevents psoriasiform dermatitis in an IL-23-dependent murine model.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Role of G protein-coupled receptor kinase-6 inPhysiological genomics · 2017Article
- Regulation of Chemokine Signal Integration by Activator of G-Protein Signaling 4 (AGS4).The Journal of pharmacology and experimental therapeutics · 2017Article
- Modulation of infection-mediated migration of neutrophils and CXCR2 trafficking by osteopontin.Immunology · 2017Article
- The impact of RGS and other G-protein regulatory proteins on Gαi-mediated signaling in immunity.Biochemical pharmacology · 2016Review
- Blunted apoptosis of erythrocytes in mice deficient in the heterotrimeric G-protein subunit Gαi2.Scientific reports · 2016Article
- Regulation of Airway Inflammation by G-protein Regulatory Motif Peptides of AGS3 protein.Scientific reports · 2016Article
- Activator of G-Protein Signaling 3-Induced Lysosomal Biogenesis Limits Macrophage Intracellular Bacterial Infection.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The IL-8 (CXCL8) receptors CXCR1 and CXCR2 couple to Gαi to induce leukocyte recruitment and activation at sites of inflammation. We recently showed that CXCR1 couples predominantly to the G protein-coupled receptor kinase (GRK)2, whereas CXCR2 interacts with GRK6 to regulate cellular responses. In addition to G protein-coupled receptors, GRKs displayed a more diverse protein/protein interaction in cells. In this study, we sought to identify GRK6 binding partner(s) that may influence CXCL8 activities, using RBL-2H3 cells stably expressing CXCR1 (RBL-CXCR1) or CXCR2 (RBL-CXCR2), as well as human and murine neutrophils. Our data demonstrated that, upon CXCR2 activation, GRK6 interacts with activator of G protein signaling (AGS)3 and Gαi2 to form a GRK6/AGS3/Gαi2 complex. This complex is time dependent and peaked at 2-3 min postactivation. GTPγS pretreatment blocked GRK6/AGS3/Gαi2 formation, suggesting that this assembly depends on G protein activation. Surprisingly, CXCR2 activation induced AGS3 phosphorylation in a PKC-dependent, but GRK6-independent, fashion. Overexpression of AGS3 in RBL-CXCR2 significantly inhibited CXCL8-induced Ca(2+) mobilization, phosphoinositide hydrolysis, and chemotaxis. In contrast, short hairpin RNA inhibition of AGS3 enhanced CXCL8-induced Ca(2+) mobilization, receptor resistance to desensitization, and recycling to the cell surface, with no effect on receptor internalization. Interestingly, RBL-CXCR2-AGS3(-/-) cells displayed a significant increase in CXCR2 expression on the cell surface but decreased ERK1/2 and P38 MAPK activation. Taken together, these results indicate that GRK6 complexes with AGS3-Gαi2 to regulate CXCR2-mediated leukocyte functions at different levels, including downstream effector activation, receptor trafficking, and expression at the cell membrane.
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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.