phosphatasemediated

Phosphatase-mediated refers to processes and regulatory mechanisms that rely on phosphatases, enzymes that catalyze the hydrolysis of phosphate groups from substrates such as proteins, lipids, and nucleotides. Through dephosphorylation, phosphatases reverse phosphorylation signals and thereby modulate enzyme activity, protein interactions, localization, and stability.

The primary enzyme classes include protein tyrosine phosphatases (PTPs), serine/threonine phosphatases (PP1, PP2A, PP2B/calcineurin, PP2C), and dual-specificity phosphatases (DUSPs) that remove phosphates from both tyrosine and serine/threonine residues. Lipid phosphatases, notably PTEN, remove phosphate groups from phosphoinositides, influencing membrane signaling. Alkaline phosphatases hydrolyze phosphate from a variety of substrates extracellularly.

Mechanistically, many protein phosphatases use active-site residues such as cysteine (PTPs) or metal ions (Mg2+/Mn2+) in serine/threonine phosphatases. Regulation occurs via calcium, calmodulin, scaffolding proteins, subunit composition, and localization. Dephosphorylation often counteracts kinase activity, but can also activate certain substrates, as in NFAT activation after calcineurin-mediated dephosphorylation.

Functionally, phosphatase-mediated signaling governs cell cycle control, metabolism, neuronal signaling, and immune responses. Dysregulation is associated with cancer, metabolic diseases, and neurodegeneration. Pharmacological agents targeting phosphatases are under development, though selectivity remains a challenge; phosphatase activity is commonly assessed with phosphatase inhibitors or phosphoproteomics.