Chemokine receptors – Exemplifying functional divergence in G protein-coupled receptors

Abstract

G protein-coupled receptors are known for their ability to generate a wide range of functional responses through interaction with various intracellular partners. This versatility is particularly evident within the chemokine receptor family, where conventional receptors signal primarily through classic G protein-coupled pathways while atypical chemokine receptors appear not to possess such ability but instead couple to alternative intracellular partners such as β-arrestins. Functional diversity in signaling presents unique opportunities for drug development, allowing different pathways to be selectively targeted to meet specific therapeutic needs. This minireview explores the mechanisms by which G protein-coupled receptor signaling, particularly within the chemokine receptor family, can be diversified at the modulatory, transmembrane, and intracellular levels. Significance Statement: This minireview explores how signaling in the chemokine receptor family diversifies at the ligand, transmembrane, and intracellular levels. This functional diversity presents unique opportunities for drug development by selectively targeting distinct pathways.