ReviewFrontiers in immunology2014
Biased and g protein-independent signaling of chemokine receptors.
Review in Frontiers in immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 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.
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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
98 citing papers in PubMed, 177 citations in OpenAlex.
- Single-Cell Pan-Cancer Atlas Reveals GPR171 as a Candidate Marker of CD8International journal of molecular sciences · 2026Article
- Receptor dimerization enables ligand discrimination through tunable response heterogeneity.PLoS computational biology · 2025Article
- CX3CL1/CX3CR1 involved modulation of microglial activation and eosinophilic meningoencephalitis in angiostrongyliasis.Food and waterborne parasitology · 2025Article
- CXCR3-mediated natural killer cell infiltration exacerbates white matter injury after intracerebral haemorrhage.Brain : a journal of neurology · 2025Article
- Noncanonical roles of chemokine regions in CCR9 activation revealed by structural modeling and mutational mapping.Nature communications · 2025Article
- Encoding and decoding selectivity and promiscuity in the human chemokine-GPCR interaction network.Cell · 2025Article
- Why Are Cytomegalovirus-Encoded G-Protein-Coupled Receptors Essential for Infection but Only Variably Conserved?Pathogens (Basel, Switzerland) · 2025Review
- Chemokines in the resolution of inflammation: key players and targets for therapeutic modulation.Frontiers in immunology · 2025Review
- Chemokine Receptor N-Terminus Charge Dictates Reliance on Post-Translational Modifications for Effective Ligand Capture and Following Boosting by Defense Peptides.International journal of molecular sciences · 2024Article
- Cyclic Adenosine Monophosphate Signaling in Chronic Kidney Disease: Molecular Targets and Therapeutic Potentials.International journal of molecular sciences · 2024Review
- CC Chemokine Family Members' Modulation as a Novel Approach for Treating Central Nervous System and Peripheral Nervous System Injury-A Review of Clinical and Experimental Findings.International journal of molecular sciences · 2024Review
- Unveiling the structural mechanisms of nonpeptide ligand recognition and activation in human chemokine receptor CCR8.Science advances · 2024Article
- Chemokine Receptor Profile of T Cells and Progression Rate of Geographic Atrophy Secondary to Age-related Macular Degeneration.Investigative ophthalmology & visual science · 2024Observational
- Chemokines form complex signals during inflammation and disease that can be decoded by extracellular matrix proteoglycans.Science signaling · 2023Article
- Chemokine binding to PSGL-1 is controlled by O-glycosylation and tyrosine sulfation.Cell chemical biology · 2023Article
- Identification of a Salt Bridge That Is Functionally Important for Chemokine Receptor CXCR1 but not CXCR2.ACS pharmacology & translational science · 2023Article
- Molecular insights into intrinsic transducer-coupling bias in the CXCR4-CXCR7 system.Nature communications · 2023Article
- CCR7 Mediates Cell Invasion and Migration in Extrahepatic Cholangiocarcinoma by Inducing Epithelial-Mesenchymal Transition.Cancers · 2023Article
- Discovery of Bis-Imidazoline Derivatives as New CXCR4 Ligands.Molecules (Basel, Switzerland) · 2023Article
- Physiology of chemokines in the cancer microenvironment.American journal of physiology. Cell physiology · 2023Review
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Biased signaling or functional selectivity occurs when a 7TM-receptor preferentially activates one of several available pathways. It can be divided into three distinct forms: ligand bias, receptor bias, and tissue or cell bias, where it is mediated by different ligands (on the same receptor), different receptors (with the same ligand), or different tissues or cells (for the same ligand-receptor pair). Most often biased signaling is differentiated into G protein-dependent and β-arrestin-dependent signaling. Yet, it may also cover signaling differences within these groups. Moreover, it may not be absolute, i.e., full versus no activation. Here we discuss biased signaling in the chemokine system, including the structural basis for biased signaling in chemokine receptors, as well as in class A 7TM receptors in general. This includes overall helical movements and the contributions of micro-switches based on recently published 7TM crystals and molecular dynamics studies. All three forms of biased signaling are abundant in the chemokine system. This challenges our understanding of "classic" redundancy inevitably ascribed to this system, where multiple chemokines bind to the same receptor and where a single chemokine may bind to several receptors - in both cases with the same functional outcome. The ubiquitous biased signaling confers a hitherto unknown specificity to the chemokine system with a complex interaction pattern that is better described as promiscuous with context-defined roles and different functional outcomes in a ligand-, receptor-, or cell/tissue-defined manner. As the low number of successful drug development plans implies, there are great difficulties in targeting chemokine receptors; in particular with regard to receptor antagonists as anti-inflammatory drugs. Un-defined and putative non-selective targeting of the complete cellular signaling system could be the underlying cause of lack of success. Therefore, biased ligands could be the solution.
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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.