Toxicology G Protein - Coupled Receptor Kinases

The importance of G protein-coupled receptor (GPCR) kinases (GRKs) as regulators of GPCR signaling has been widely recognized. In humans, GRKs constitute a family of seven protein kinases involved in the phosphorylation and desensitization of agonist-activated GPCRs in many physiological processes. The GPCR desensitization process is initiated by GRKs, but involves several subsequent steps including arrestin capping of phosphorylated receptors. High-resolution crystal structures were determined for four members of the GRK family, i.e., GRK1, GRK2, GRK5, and GRK6. This allowed decoding of the molecular basis of GRK activation and interactions with GPCR substrates, as well as the GRK interactions with cellular membranes and inhibitors. Here, we focused on retinal GRKs, or photopigment kinases, rhodopsin kinase (GRK1), and GRK7, in the context of major general advances in the GRK fi eld.