Targeted proteomics analyses of phosphorylation-dependent signalling networks

Abstract

Protein phosphorylation often regulates interactions between components of signalling networks. Its tight regulation by opposing actions of kinases and phosphatases contribute to making this modification key in controlling the dynamic architecture of phosphorylation-dependent networks. The introduction in cell signalling research of long-standing targeted proteomics approaches such as selected reaction monitoring (SRM) combined with the development of state-of-the-art methods such as parallel reaction monitoring (PRM) and data-independent analysis (DIA), have allowed delineating temporal quantitative profiles of interactions networks. This review summarizes how targeted proteomics analyses have recently contributed to our comprehension of phosphorylation-dependent protein interaction networks and proposes how these could be applied to address clinical problems. BIOLOGICAL SIGNIFICANCE: Intracellular communication and information processing are performed by context-specific protein interaction networks that are often regulated by protein phosphorylation. Quantification of dynamic changes within these signalling networks is of critical importance to understand cell biology in normal and disease states, but remains challenging. Targeted proteomics approaches have contributed greatly to our understanding of these phosphorylation-dependent signalling networks.