Agonist-selective signaling of G protein-coupled receptor: mechanisms and implications

Abstract

Agonist-selective signaling or ligand-biased signaling of G protein-coupled receptor (GPCR) has become the focus of an increasing number of laboratories. The principle of this concept is that agonist possesses different abilities to activate different signaling pathways. Current review summarizes the observations of agonist-selective signaling of various GPCRs, indicating the significance of agonist-selective signaling in biological processes. In addition, current review also provides an overview on how agonist-selective signaling is initiated. Especially, the relationship between GPCR-G protein interaction and GPCR-beta-arrestin interaction is discussed in depth.

Figure 1. Schematic representation of agonist-selective signaling

Agonist I and II exhibit differential efficacies in pathway A and B. The “Full Agonist” and “Neutral Antagonist” were used to indicate the different “intrinsic efficacies” of these agonists on the two pathways. Also, they can be “Partial Agonist” or “Inverse Agonist”.

Figure 2. Schematic diagram of the competition between G protein and β-arrestin

“G” and “Phos” were used to represent G protein and phosphorylation of GPCR, respectively.