dephosphorylation

Dephosphorylation is the enzymatic removal of phosphate groups from molecules, most often proteins, by phosphatases. This reaction typically involves hydrolysis of phosphoester bonds and releases inorganic phosphate. Dephosphorylation counteracts phosphorylation and regulates protein activity, conformation, interactions, and subcellular localization, making it a key control point in cellular signaling networks.

Protein phosphatases are the main enzymes that catalyze dephosphorylation. They are classified primarily as serine/threonine phosphatases (such as PP1, PP2A, PP2B/calcineurin, and PP2C), tyrosine phosphatases (PTPs), and dual-specificity phosphatases (DUSPs) that target both serine/threonine and tyrosine residues. Receptor-type protein tyrosine phosphatases act at the cell surface. Phosphatase activity is regulated by metal ions (typically Mg2+ or Mn2+), regulatory subunits, subcellular localization, and, in some cases, calcium/calmodulin signaling.

Biologically, dephosphorylation serves to terminate or fine-tune phosphorylation-dependent signaling, controlling processes such as the cell cycle, metabolism, gene expression, and neuronal signaling. Dysregulation of phosphatases or their substrates is linked to diseases including cancer, diabetes, neurodegenerative disorders, and autoimmune conditions. Lipid phosphatases (for example, PTEN) illustrate the diversity of targets, removing phosphate groups from phosphoinositides as well as proteins.

Methods to study dephosphorylation include phosphatase activity assays, phosphoproteomics to map phosphorylation sites, and substrate-trapping mutants to identify physiological targets. Overall, dephosphorylation acts as the essential counterbalance to kinase-driven phosphorylation in cellular regulation.