ArticleThe Journal of biological chemistry2013
The chemokine receptor CCR1 is constitutively active, which leads to G protein-independent, β-arrestin-mediated internalization.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 92 citations in OpenAlex.
- Chemokine receptor CCR1 restrains adipose tissue remodelling via cAMP/PKA/CREB signalling and adipocyte‒macrophage crosstalk in mice.Clinical and translational medicine · 2026Article
- Elevated conformational dynamics makes ACKR3 activation-prone and G protein-incompetent.bioRxiv : the preprint server for biology · 2026Article
- Monocyte Migration Emerges from a Divergent Chemokine Signaling Network.bioRxiv : the preprint server for biology · 2026Article
- Evolution of CCR1 and CCR1L1 reveals complex duplication scenarios in Muroids and Ruminants.Immunogenetics · 2026Article
- Mechanisms of Pertussis Toxin Action: ADP-Ribosylation and Its Role in Pertussis Pathogenesis.Toxins · 2026Review
- Inhibition of constitutive activity of the atypical chemokine receptor 3 by the small-molecule inverse agonist VUF16840.Molecular pharmacology · 2025Article
- Noncanonical roles of chemokine regions in CCR9 activation revealed by structural modeling and mutational mapping.Nature communications · 2025Article
- Novel immunotargets in multiple myeloma: biological relevance and therapeutic potential.Biomarker research · 2025Review
- Article
- Traffic control: Mechanisms of ligand-specific internalization and intracellular distribution of CCR5.Molecular pharmacology · 2025Article
- Endosomal chemokine receptor signalosomes regulate central mechanisms underlying cell migration.eLife · 2025Article
- Essential strategies for the detection of constitutive and ligand-dependent Gi-directed activity of 7TM receptors using bioluminescence resonance energy transfer.bioRxiv : the preprint server for biology · 2024Article
- Targeting cytokine networks in neuroinflammatory diseases.Nature reviews. Drug discovery · 2024Review
- Fluorophore-Labeled Pyrrolones Targeting the Intracellular Allosteric Binding Site of the Chemokine Receptor CCR1.ACS pharmacology & translational science · 2024Article
- Beneath the surface: endosomal GPCR signaling.Trends in biochemical sciences · 2024Review
- Location bias: A "Hidden Variable" in GPCR pharmacology.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Review
- Upregulation of Inflammatory Mediators in Peripheral Blood CD40International journal of molecular sciences · 2023Article
- The dual-function chemokine receptor CCR2 drives migration and chemokine scavenging through distinct mechanisms.Science signaling · 2023Article
- Chemokine CXCL4 interactions with extracellular matrix proteoglycans mediate widespread immune cell recruitment independent of chemokine receptors.Cell reports · 2023Article
- Evolutionary analyses reveal immune cell receptor GPR84 as a conserved receptor for bacteria-derived molecules.iScience · 2022Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Activation of G protein-coupled receptors by their associated ligands has been extensively studied, and increasing structural information about the molecular mechanisms underlying ligand-dependent receptor activation is beginning to emerge with the recent expansion in GPCR crystal structures. However, some GPCRs are also able to adopt active conformations in the absence of agonist binding that result in the initiation of signal transduction and receptor down-modulation. In this report, we show that the CC-type chemokine receptor 1 (CCR1) exhibits significant constitutive activity leading to a variety of cellular responses. CCR1 expression is sufficient to induce inhibition of cAMP formation, increased F-actin content, and basal migration of human and murine leukocytes. The constitutive activity leads to basal phosphorylation of the receptor, recruitment of β-arrestin-2, and subsequent receptor internalization. CCR1 concurrently engages Gαi and β-arrestin-2 in a multiprotein complex, which may be accommodated by homo-oligomerization or receptor clustering. The data suggest the presence of two functional states for CCR1; whereas receptor coupled to Gαi functions as a canonical GPCR, albeit with high constitutive activity, the CCR1·β-arrestin-2 complex is required for G protein-independent constitutive receptor internalization. The pertussis toxin-insensitive uptake of chemokine by the receptor suggests that the CCR1·β-arrestin-2 complex may be related to a potential scavenging function of the receptor, which may be important for maintenance of chemokine gradients and receptor responsiveness in complex fields of chemokines during inflammation.
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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.