Regulation of the pro-inflammatory G protein-coupled receptor GPR84

Br J Pharmacol. 2024 May;181(10):1500-1508. doi: 10.1111/bph.16098. Epub 2023 May 11.

Abstract

GPR84 is an understudied rhodopsin-like class A G protein-coupled receptor, which is arousing particular interest from a therapeutic perspective. Not least this reflects that gpr84 expression is significantly up-regulated following acute inflammatory stimuli and in inflammatory diseases, and that receptor activation plays a role in regulating pro-inflammatory responses and migration of cells of the innate immune system such as neutrophils, monocytes, macrophages and microglia. Although most physiological responses of GPR84 reflect receptor coupling to Gαi/o-proteins, several studies indicate that agonist-activated GPR84 can recruit arrestin adaptor proteins and this regulates receptor internalisation and desensitisation. To date, little is known on the patterns of either basal or ligand regulated GPR84 phosphorylation and how these might control these processes. Here, we consider what is known about the regulation of GPR84 signalling with a focus on how G protein receptor kinase-mediated phosphorylation regulates arrestin protein recruitment and receptor function. LINKED ARTICLES: This article is part of a themed issue GPR84 Pharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.10/issuetoc.

Keywords: GPCR phosphorylation; GPCR regulation; GPR84; GRKs.

Publication types

  • Review

MeSH terms

  • Arrestin / metabolism
  • Humans
  • Macrophages / metabolism
  • Phosphorylation
  • Receptors, G-Protein-Coupled* / metabolism
  • Signal Transduction*

Substances

  • Arrestin
  • GPR84 protein, human
  • Receptors, G-Protein-Coupled