PhosphorylierungsKaskaden

Phosphorylation is a biochemical process in which a phosphate group is covalently added to a molecule, typically from ATP, altering the substrate's properties. In cells, protein phosphorylation is the most studied form and serves as a dynamic regulatory mechanism that can activate or inhibit enzymes, change protein interactions, or modify localization. The phosphate donor is usually ATP, and the reaction is catalyzed by enzymes called kinases. Removal of phosphate groups is carried out by phosphatases, making phosphorylation a reversible switch integral to cellular signaling and metabolism.

In eukaryotes, protein phosphorylation most commonly occurs on serine and threonine residues, and to a lesser extent on tyrosine. In some bacteria and lower organisms, histidine phosphorylation is prominent. Phosphorylation can create docking sites for other proteins, alter enzyme conformation, or modulate activity. Phosphorylation cascades, in which one kinase activates another, amplify signals and coordinate responses to stimuli. Phosphorylation can regulate cell cycle progression, transcription, membrane transport, and metabolic pathways.

Disruption of phosphorylation balance is linked to diseases such as cancer and diabetes, making kinases and phosphatases important drug targets. Detection and study rely on mass spectrometry, phospho-specific antibodies, and phosphoproteomics to map phosphorylation sites and quantify their dynamics. The concept dates to mid-20th century work on enzyme regulation; notable researchers Edmond Fischer and Edwin Krebs helped establish protein phosphorylation as a central regulatory mechanism, earning a Nobel Prize in 1992.