selfphosphorylation

Selfphosphorylation, or autophosphorylation, is the process by which a protein kinase transfers a phosphate group from ATP to one of its own amino acid residues. This can occur in cis, within a single molecule, or in trans, between two molecules of the same kinase. In cis autophosphorylation, the activation loop or other regulatory segments become phosphorylated, often leading to conformational changes that increase catalytic activity. In trans autophosphorylation, two kinase molecules phosphorylate each other, a mechanism common in receptor tyrosine kinases upon ligand-induced dimerization.

Residues modified include serine, threonine, and tyrosine, with the specific residue determining the effect on activity and signaling interactions. Autophosphorylation can promote catalytic activation, create docking sites for SH2 or other phospho-recognition domains, alter substrate specificity, change subcellular localization, or contribute to feedback regulation. However, not all autophosphorylation events activate kinases; some serve regulatory purposes or mark the kinase for degradation.

Examples: many receptor tyrosine kinases autophosphorylate on multiple tyrosine residues in their cytoplasmic tails after ligand binding, generating binding sites for downstream signaling proteins. Src family kinases undergo trans-autophosphorylation on Tyr416 that enhances activity, while phosphorylation on Tyr527 by other kinases can suppress activity. Methods to study autophosphorylation include mass spectrometry, phospho-specific antibodies, and mutational analysis of phosphorylation sites. Dysregulation of autophosphorylation is implicated in diseases such as cancer, making it a target for therapeutic inhibitors.