Matches in SemOpenAlex for { <https://semopenalex.org/work/W2901815433> ?p ?o ?g. }
- W2901815433 endingPage "80" @default.
- W2901815433 startingPage "69" @default.
- W2901815433 abstract "Chemokines play crucial roles in combating microbial infection and initiating tissue repair by recruiting neutrophils in a timely and coordinated manner. In humans, no less than seven chemokines (CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, and CXCL8) and two receptors (CXCR1 and CXCR2) mediate neutrophil functions but in a context dependent manner. Neutrophil-activating chemokines reversibly exist as monomers and dimers, and their receptor binding triggers conformational changes that are coupled to G-protein and β-arrestin signaling pathways. G-protein signaling activates a variety of effectors including Ca2+ channels and phospholipase C. β-arrestin serves as a multifunctional adaptor and is coupled to several signaling hubs including MAP kinase and tyrosine kinase pathways. Both G-protein and β-arrestin signaling pathways play important non-overlapping roles in neutrophil trafficking and activation. Functional studies have established many similarities but distinct differences for a given chemokine and between chemokines at the level of monomer vs. dimer, CXCR1 vs. CXCR2 activation, and G-protein vs. β-arrestin pathways. We propose that two forms of the ligand binding two receptors and activating two signaling pathways enables fine-tuned neutrophil function compared to a single form, a single receptor, or a single pathway. We summarize the current knowledge on the molecular mechanisms by which chemokine monomers/dimers activate CXCR1/CXCR2 and how these interactions trigger G-protein/β-arrestin-coupled signaling pathways. We also discuss current challenges and knowledge gaps, and likely advances in the near future that will lead to a better understanding of the relationship between the chemokine-CXCR1/CXCR2-G-protein/β-arrestin axis and neutrophil function." @default.
- W2901815433 created "2018-11-29" @default.
- W2901815433 creator A5006530891 @default.
- W2901815433 creator A5027784658 @default.
- W2901815433 creator A5042613793 @default.
- W2901815433 creator A5071880479 @default.
- W2901815433 date "2019-02-01" @default.
- W2901815433 modified "2023-10-16" @default.
- W2901815433 title "How do chemokines navigate neutrophils to the target site: Dissecting the structural mechanisms and signaling pathways" @default.
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