ArticleJournal of leukocyte biology2013
G protein-coupled receptor kinase-3-deficient mice exhibit WHIM syndrome features and attenuated inflammatory responses.
Article in Journal of leukocyte biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- G-Protein-Coupled Receptor Kinase 2 Limits CCL21-Induced T Cell Migration via Phospholipase Cγ1.Receptors (Basel, Switzerland) · 2025Article
- Unveiling WHIM syndrome: Mavorixafor's emerging role in immune restoration and therapy.Clinical and experimental immunology · 2025Review
- Expanding CXCR4 variant landscape in WHIM syndrome: integrating clinical and functional data for variant interpretation.Frontiers in immunology · 2024Review
- Article
- G protein-coupled receptor kinase 3 modulates mesenchymal stem cell proliferation and differentiation through sphingosine-1-phosphate receptor regulation.Stem cell research & therapy · 2022Article
- Light-Triggered Drug Release from Red Blood Cells Suppresses Arthritic Inflammation.Advanced therapeutics · 2022Article
- Combinatorial depletions of G-protein coupled receptor kinases in immune cells identify pleiotropic and cell type-specific functions.Frontiers in immunology · 2022Article
- GRK3 deficiency elicits brain immune activation and psychosis.Molecular psychiatry · 2021Article
- Neutrophils self-limit swarming to contain bacterial growth in vivo.Science (New York, N.Y.) · 2021Article
- Review
- Chemerin-activated functions of CMKLR1 are regulated by G protein-coupled receptor kinase 6 (GRK6) and β-arrestin 2 in inflammatory macrophages.Molecular immunology · 2019Article
- 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
- G Protein-Coupled Receptor Kinase 3 and Protein Kinase C Phosphorylate the Distal C-Terminal Tail of the Chemokine Receptor CXCR4 and Mediate Recruitment ofMolecular pharmacology · 2017Article
- Dysplasia of Granulocytes in a Patient with HPV Disease, Recurrent Infections, and B Lymphopenia: A Novel Variant of WHIM Syndrome?Frontiers in pediatrics · 2017Article
- Pathogenesis, diagnosis and therapeutic strategies in WHIM syndrome immunodeficiency.Expert opinion on orphan drugs · 2017Article
- Overexpression of GRK3, Promoting Tumor Proliferation, Is Predictive of Poor Prognosis in Colon Cancer.Disease markers · 2017Article
- G Protein-Coupled Receptor Kinases in the Inflammatory Response and Signaling.Advances in immunology · 2017Review
- G Protein Coupled Receptor Kinase 3 Regulates Breast Cancer Migration, Invasion, and Metastasis.PloS one · 2016Article
- Functional consequences of perturbed CXCL12 signal processing: analyses of immature hematopoiesis in GRK6-deficient mice.Stem cells and development · 2015Article
- Targeting the molecular and cellular interactions of the bone marrow niche in immunologic disease.Current allergy and asthma reports · 2014Review
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
Chemokine receptor interactions coordinate leukocyte migration in inflammation. Chemokine receptors are GPCRs that when activated, are phosphorylated by GRKs to turn off G protein-mediated signaling yet recruit additional signaling machinery. Recently, GRK3 was identified as a negative regulator of CXCL12/CXCR4 signaling that is defective in human WHIM syndrome. Here, we report that GRK3-/- mice exhibit numerous features of human WHIM, such as impaired CXCL12-mediated desensitization, enhanced CXCR4 signaling to ERK activation, altered granulocyte migration, and a mild myelokathexis. Moreover, GRK3-/- protects mice from two acute models of inflammatory arthritis (K/BxN serum transfer and CAIA). In these granulocyte-dependent disease models, protection of GRK3-/- mice is mediated by retention of cells in the marrow, fewer circulating granulocytes in the peripheral blood, and reduced granulocytes in the joints during active inflammation. In contrast to WHIM, GRK3-/- mice have minimal hypogammaglobulinemia and a peripheral leukocytosis with increased lymphocytes and absent neutropenia. Thus, we conclude that the loss of GRK3-mediated regulation of CXCL12/CXCR4 signaling contributes to some, but not all, of the complete WHIM phenotype and that GRK3 inhibition may be beneficial in the treatment of inflammatory arthritis.
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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.