Phosphataseis

Phosphataseis are enzymes that catalyze the removal of phosphate groups (dephosphorylation) from proteins, lipids, and small molecules. By reversing phosphorylation, they modulate signaling pathways, metabolic flux, and cellular processes. They act opposite to kinases and help reset cellular states after stimulation.

Protein phosphatases remove phosphate from amino acids and are categorized into protein tyrosine phosphatases (PTPs), serine/threonine phosphatases (PSPs) such as PP1, PP2A, and calcineurin (PP2B), and dual-specificity phosphatases (DUSPs) that act on both tyrosine and serine/threonine residues. Lipid phosphatases remove phosphate from lipid substrates, with examples including PTEN and SHIP1/2 that regulate phosphoinositide signaling.

Most phosphatases require metal cofactors such as magnesium or manganese. Substrate specificity arises from active-site motifs, regulatory subunits, and cellular localization. Some phosphatases are regulated by calcium/calmodulin, phosphorylation, or interactions with scaffolding proteins, which alter activity or targeting.

Phosphataseis control numerous physiological processes, including cell cycle progression, metabolism, neuronal signaling, and immune responses. Dysregulation or mutations in phosphatases are associated with cancer, metabolic diseases, and neurodegenerative disorders. Inhibitors and modulators of phosphatases are active areas of therapeutic research, though achieving high specificity is challenging.

The term phosphatase derives from Greek roots for phosphate and enzyme. In research, phosphatase activity is commonly measured by assays that detect phosphate release, such as p-nitrophenyl phosphate dephosphorylation or malachite green assays, and by genetic and pharmacological tools.