Unravelling G protein-coupled receptor signalling networks using global phosphoproteomics

Abstract

G protein-coupled receptor (GPCR) activation initiates signalling via a complex network of intracellular effectors that combine to produce diverse cellular and tissue responses. Although we have an advanced understanding of the proximal events following receptor stimulation, the molecular detail of GPCR signalling further downstream often remains obscure. Unravelling these GPCR-mediated signalling networks has important implications for receptor biology and drug discovery. In this context, phosphoproteomics has emerged as a powerful approach for investigating global GPCR signal transduction. Here, we provide a brief overview of the phosphoproteomic workflow and discuss current limitations and future directions for this technology. By highlighting some of the novel insights into GPCR signalling networks gained using phosphoproteomics, we demonstrate the utility of global phosphoproteomics to dissect GPCR signalling networks and to accelerate discovery of new targets for therapeutic development.

Keywords: G protein-coupled receptor; ligands; mass spectrometry; phosphoproteomics; signalling networks.