Phosphorylation

Phosphorylation is a chemical reaction that attaches a phosphate group to a molecule. In cells the phosphate usually comes from ATP, and the transfer is catalyzed by enzymes called kinases; phosphatases remove it again, a reaction called dephosphorylation. ATP is itself made by phosphorylating ADP, in mitochondria by oxidative phosphorylation, in chloroplasts by photophosphorylation and during glycolysis by substrate-level phosphorylation. Sugars are phosphorylated too: the first step of glycolysis adds a phosphate to glucose, trapping it inside the cell.

In proteins, kinases add phosphate to the side chains of serine, threonine or tyrosine. The bulky, negatively charged group changes the protein's shape or which partners it binds, switching its activity on or off within seconds. Chains of kinases activating one another, called phosphorylation cascades, relay signals from receptors at the cell surface, such as the receptor tyrosine kinases for growth factors, to targets inside the cell. Phosphorylation also drives the cell cycle and controls enzymes of metabolism.

Overactive kinases drive many cancers, so kinase inhibitors such as imatinib, used for chronic myeloid leukemia, form a major class of targeted drugs. In proteomics, phosphorylation is one of the most studied post-translational modifications, tracked with phospho-specific antibodies or mass spectrometry.