Dephosphorylated

Dephosphorylated describes the state of a molecule from which one or more phosphate groups have been removed. In biology, phosphorylation adds a phosphate group to proteins, lipids, or other substrates, often altering activity, interactions, or localization. Dephosphorylation is the hydrolytic removal of these phosphate groups, typically releasing inorganic phosphate (Pi). The process is essential for turning off or modulating signaling events initiated by kinases.

Enzymes called phosphatases carry out dephosphorylation. The main classes are protein phosphatases, including serine/threonine phosphatases (for example PP1, PP2A, PP2B/calcineurin, PP2C) and tyrosine phosphatases, and dual-specificity phosphatases that act on both residues. Other enzymes remove phosphate groups from non-protein substrates (lipids, nucleotides). Phosphatases require metal cofactors such as Mg2+ or Mn2+, and their activity is regulated by regulatory subunits, substrates, inhibitors, and cellular signals.

Functionally, dephosphorylation serves as a counterbalance to phosphorylation, shaping signal transduction networks, metabolism, the cell cycle, and apoptosis. It can change a protein’s conformation, catalytic activity, interaction partners, or subcellular localization. Dephosphorylation is spatially and temporally controlled, occurring throughout the cytosol, nucleus, and organelles, and often follows specific phospho-kinase cascades.

Clinically, abnormal phosphatase activity is linked to diseases such as cancer, metabolic disorders, and neurodegeneration. Pharmacological modulation of phosphatases—such as calcineurin inhibitors cyclosporine and tacrolimus—affects immune signaling. Analytical approaches include phosphoproteomics to map phosphorylation states, and enzymatic assays using substrates like p-nitrophenyl phosphate to measure phosphatase activity.