Autophosphorylating

Autophosphorylating is the biochemical process by which a protein kinase catalyzes the transfer of a phosphate group from ATP to one of its own amino acid residues, typically serine, threonine, or tyrosine. In many contexts the term also covers phosphorylation of a second molecule of the same enzyme in close proximity, a phenomenon known as trans-autophosphorylation; by contrast, cis-autophosphorylation occurs within the same polypeptide.

In receptor and non-receptor tyrosine kinases, autophosphorylating often follows dimerization or activation, enabling full catalytic activity and the creation of phosphotyrosine docking sites for downstream signaling proteins. In bacterial two-component systems, sensor histidine kinases autophosphorylate on a histidine residue using ATP, a modification that is subsequently transferred to a response regulator.

Biological significance: autophosphorylating can modulate enzymatic activity, substrate specificity, and interaction with adaptor proteins. It acts as a switch that turns on signaling cascades, and it can serve as a feedback mechanism or a stabilization step for signaling complexes.

Examples include epidermal growth factor receptor (EGFR) family receptors that autophosphorylate on multiple tyrosines upon ligand binding, and Src-family kinases that undergo activation loop autophosphorylation. Bacterial histidine kinases such as EnvZ autophosphorylate on histidine to regulate osmoregulation.

Measurement and regulation: autophosphorylating depends on ATP and divalent cations like Mg2+. It is regulated by conformational changes, protein–protein interactions, and cellular localization, and is commonly studied by in vitro kinase assays and phosphosite mapping.