ArticleThe Journal of clinical investigation2008
Leukocyte analysis from WHIM syndrome patients reveals a pivotal role for GRK3 in CXCR4 signaling.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
72 citing papers in PubMed, 131 citations in OpenAlex.
- Trial
- Unveiling WHIM syndrome: Mavorixafor's emerging role in immune restoration and therapy.Clinical and experimental immunology · 2025Review
- CXCR4: from B-cell development to B cell-mediated diseases.Life science alliance · 2024Review
- Expanding CXCR4 variant landscape in WHIM syndrome: integrating clinical and functional data for variant interpretation.Frontiers in immunology · 2024Review
- The complex nature of CXCR4 mutations in WHIM syndrome.Frontiers in immunology · 2024Review
- Vesicle-associated membrane protein 2 is a cargo-selective v-SNARE for a subset of GPCRs.The Journal of cell biology · 2023Article
- Reduced G protein signaling despite impaired internalization and β-arrestin recruitment in patients carrying a CXCR4Leu317fsX3 mutation causing WHIM syndrome.JCI insight · 2023Article
- G protein-coupled receptor signaling: transducers and effectors.American journal of physiology. Cell physiology · 2022Review
- Altered CXCR4 dynamics at the cell membrane impairs directed cell migration in WHIM syndrome patients.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- G protein-coupled receptor kinase 3 modulates mesenchymal stem cell proliferation and differentiation through sphingosine-1-phosphate receptor regulation.Stem cell research & therapy · 2022Article
- GRK3 deficiency elicits brain immune activation and psychosis.Molecular psychiatry · 2021Article
- The negative charge of the 343 site is essential for maintaining physiological functions of CXCR4.BMC molecular and cell biology · 2021Article
- Review
- Predicting Human Protein Subcellular Locations by Using a Combination of Network and Function Features.Frontiers in genetics · 2021Article
- Aberrant CXCR4 Signaling at Crossroad of WHIM Syndrome and Waldenstrom's Macroglobulinemia.International journal of molecular sciences · 2020Review
- New Insights on the Emerging Genomic Landscape of CXCR4 in Cancer: A Lesson from WHIM.Vaccines · 2020Review
- β-Arrestin1 and β-Arrestin2 Are Required to Support the Activity of the CXCL12/HMGB1 Heterocomplex on CXCR4.Frontiers in immunology · 2020Article
- A chemotaxis model to explain WHIM neutrophil accumulation in the bone marrow of WHIM mouse model.Blood science (Baltimore, Md.) · 2019Article
- WHIM Syndrome: from Pathogenesis Towards Personalized Medicine and Cure.Journal of clinical immunology · 2019Review
- Kinase activity is impaired in neutrophils of sepsis patients.Haematologica · 2019Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leukocytes from individuals with warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome, a rare immunodeficiency, and bearing a wild-type CXCR4 ORF (WHIM(WT)) display impaired CXCR4 internalization and desensitization upon exposure to CXCL12. The resulting enhanced CXCR4-dependent responses, including chemotaxis, probably impair leukocyte trafficking and account for the immunohematologic clinical manifestations of WHIM syndrome. We provided here evidence that GPCR kinase-3 (GRK3) specifically regulates CXCL12-promoted internalization and desensitization of CXCR4. GRK3-silenced control cells displayed altered CXCR4 attenuation and enhanced chemotaxis, as did WHIM(WT) cells. These findings identified GRK3 as a negative regulator of CXCL12-induced chemotaxis and as a candidate responsible for CXCR4 dysfunction in WHIM(WT) leukocytes. Consistent with this, we showed that GRK3 overexpression in both leukocytes and skin fibroblasts from 2 unrelated WHIM(WT) patients restored CXCL12-induced internalization and desensitization of CXCR4 and normalized chemotaxis. Moreover, we found in cells derived from one patient a profound and selective decrease in GRK3 products that probably resulted from defective mRNA synthesis. Taken together, these results have revealed a pivotal role for GRK3 in regulating CXCR4 attenuation and have provided a mechanistic link between the GRK3 pathway and the CXCR4-related WHIM(WT) disorder.
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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.