Modulating GPCR and 14-3-3 protein interactions: Prospects for CNS drug discovery

The activation of G-protein-coupled receptors (GPCRs) triggers a series of protein–protein interaction events that subsequently induce a chain of reactions, including alteration of receptor structures, phosphorylation, recruitment of associated proteins, protein trafficking and gene expression. Multiple GPCR signaling transduction pathways are evident – two well-studied pathways are the GPCR-mediated G-protein and β-arrestin pathways. Recently, ligand-induced interactions between GPCRs and 14-3-3 proteins have been demonstrated. This linking of GPCRs to 14-3-3 protein signal hubs opens up a whole new realm of signal transduction possibilities. 14-3-3 proteins play a key part in GPCR trafficking and signal transduction. GPCR-mediated 14-3-3 protein signaling can be harnessed for the study of GPCR function and therapeutics.