Emerging insights into serine/threonine-specific phosphoprotein phosphatase function and selectivity.

Protein phosphorylation on serine and threonine residues is a widely distributed post-translational modification on proteins that acts to regulate their function. Phosphoprotein phosphatases (PPPs) contribute significantly to a plethora of cellular functions through the accurate dephosphorylation of phosphorylated residues. Most PPPs accomplish their purpose through the formation of complex holoenzymes composed of a catalytic subunit with various regulatory subunits. PPP holoenzymes then bind and dephosphorylate substrates in a highly specific manner. Despite the high prevalence of PPPs and their important role for cellular function, their mechanisms of action in the cell are still not well understood. Nevertheless, substantial experimental advancements in (phospho-)proteomics, structural and computational biology have contributed significantly to a better understanding of PPP biology in recent years. This Review focuses on recent approaches and provides an overview of substantial new insights into the complex mechanism of PPP holoenzyme regulation and substrate selectivity.