autophosphorylates

Autophosphorylation is a biochemical process in which a kinase transfers a phosphate group from ATP to one of its own amino acid residues. It is a common mechanism for regulating enzyme activity and signaling pathways. Depending on the kinase, the phosphate can be added to serine, threonine, tyrosine, or histidine residues.

Autophosphorylation can occur in cis (within the same molecule) or in trans (between two kinase molecules that form a dimer or higher-order complex). Dimerization, conformational changes, or receptor activation often promote autophosphorylation, especially in receptor tyrosine kinases.

Functional consequences include activation of the kinase, creation of docking sites for downstream signaling proteins, and modulation of substrate specificity. In bacterial two-component systems, autophosphorylation on a histidine residue by a sensor kinase is followed by phosphotransfer to a response regulator.

Common examples include receptor tyrosine kinases such as EGFR, where ligand-induced autophosphorylation triggers signaling cascades, and non-receptor kinases like Src, which autophosphorylate to regulate activity. Bacterial histidine kinases such as EnvZ autophosphorylate and then transfer the phosphate to response regulators.

Regulation of autophosphorylation is critical for normal cellular signaling, and aberrant autophosphorylation is associated with diseases such as cancer. Therapeutic strategies include inhibitors that block autophosphorylation or its downstream effects.