phosphoproteins

Phosphoproteins are proteins that contain covalently attached phosphate groups, usually added by protein kinases to serine, threonine, or tyrosine residues and removed by phosphatases. Phosphorylation is a major regulatory mechanism in cells, enabling reversible control of protein activity, interactions, localization, and stability. In eukaryotes, most phosphorylation occurs on serine and threonine, with a smaller fraction on tyrosine; in prokaryotes histidine and aspartate phosphorylation are common in two-component signaling systems.

Mechanism and effects: Kinases recognize specific motifs; phosphorylation introduces negative charge, can induce conformational change, create docking sites for phospho-binding domains such as SH2 and 14-3-3 proteins, or disrupt interactions. This regulates signaling cascades (MAPK, PI3K-Akt), cell cycle progression, metabolism, transcription, and cytoskeletal dynamics. Examples: glycogen synthase is inhibited by phosphorylation; tau protein phosphorylation affects microtubule binding; many transcription factors are activated or repressed upon phosphorylation.

Detection and study: Phosphoproteomics uses mass spectrometry to identify sites; phospho-specific antibodies enable targeted detection.

Clinical relevance: Altered phosphorylation is common in diseases such as cancer, diabetes, and neurodegeneration. The study of phosphoproteins provides insight into cellular signaling networks and offers targets for therapeutic intervention.