phosphorylation

Phosphorylation is a biochemical process in which a phosphate group is covalently added to a molecule, most commonly a protein, by a kinase enzyme. The phosphate donor is typically adenosine triphosphate (ATP), with the reaction often producing adenosine diphosphate (ADP). Phosphorylation is usually reversible, with phosphatases catalyzing removal of the phosphate group, allowing dynamic regulation of the substrate’s properties.

Enzymes and substrates involved in phosphorylation show high specificity. Protein kinases several classes including serine/threonine kinases, tyrosine kinases, and dual-specificity kinases target amino acid residues such as serine, threonine, and tyrosine on proteins. In bacteria, histidine kinases participate in two-component signaling systems. Phosphorylation also occurs on lipids (for example, phosphoinositides) and sugars, forming phosphoester or phosphoanhydride bonds that alter activity or localization.

Phosphorylation regulates numerous cellular processes. It can activate or inhibit enzymes, change protein conformation, modify subcellular localization, or create binding sites for downstream signaling proteins. In signaling pathways, cascades such as MAP kinase transmit extracellular cues by sequential phosphorylation events. Phosphorylation integrates with metabolism, cell cycle control, and differentiation, and is central to many regulatory networks. Abnormal phosphorylation patterns are linked to diseases including cancer, diabetes, and neurodegenerative disorders, making kinases and phosphatases important targets for therapy.

Researchers study phosphorylation by phospho-specific antibodies, mass spectrometry-based phosphoproteomics, and other biochemical tools. The concept of reversible protein phosphorylation was established in the mid-20th century, earning Fischer and Krebs the Nobel Prize in Physiology or Medicine in 1992.