phosphorylations

Phosphorylations are biochemical modifications in which a phosphate group is covalently attached to a substrate. In biology, the most common donor is ATP, and the transfer is catalyzed by enzymes known as kinases. Phosphorylation can occur on proteins, lipids, and carbohydrates, and is typically reversible, with phosphatases removing the phosphate.

Protein phosphorylation is best studied in eukaryotes and most often targets serine, threonine, or tyrosine residues. In bacteria and some signaling systems, histidine and aspartate phosphorylations are common. The phosphate group changes the substrate’s charge and conformation, altering activity, interactions, localization, or stability.

Phosphorylation is central to signal transduction and metabolic regulation. It acts as a molecular switch that relays extracellular cues to intracellular responses. Major pathways include MAP kinase cascades and PI3K–AKT signaling in eukaryotes, as well as regulation of metabolic enzymes and cell cycle proteins. Dysregulation is linked to diseases such as cancer and diabetes.

Regulation and detection: Kinases and phosphatases regulate the phosphate state in a dynamic balance. Kinase families include serine/threonine, tyrosine, and dual-specificity kinases. Phosphatases provide opposite control. Studying phosphorylations employs mass spectrometry-based phosphoproteomics, phospho-specific antibodies, and radiolabeling experiments to identify sites and quantify changes.