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

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 G(alpha i/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.

Automated summary

GPR84 is a little-studied receptor that belongs to the rhodopsin-like class A G protein-coupled receptors, but it has attracted attention for its therapeutic potential. Its expression is up-regulated in response to acute inflammation and in inflammatory diseases, and activation of the receptor is involved in regulating pro-inflammatory responses and cell migration of the innate immune system. While GPR84 primarily signals through G(alpha i/o)-proteins, there is evidence that it can also recruit arrestin proteins upon agonist activation, which affects receptor internalization and desensitization. However, the phosphorylation patterns of GPR84 and their role in these processes are not well understood.