Autophosphorylation

In eukaryotes, this process occurs by the addition of a phosphate group to serine, threonine or tyrosine residues within protein kinases, normally to regulate the catalytic activity.

[3] Protein kinases, many of which are regulated by autophosphorylation, are vital in controlling the cellular proliferation, differentiation, metabolism, migration and survival.

Mutations in the genes encoding them or their potential activators or repressors can affect any number of functions within an organism.

[3] Addition of a negatively charged phosphate group brings about a change in the microenvironment that may lead to attraction or repulsion of other residues or molecules.

[3] In addition, the phosphate group yields several potential areas for hydrogen-bonding or establishment of salt-bridges, of which the latter generally involves an arginine residue.

[3] [5] Binding of effector molecules may be affected in a similar manner if the phosphorylated residue makes part of the allosteric site.

[6] The known structures include: In general, the structures of the phosphorylation of internal loops involve important domain-domain contacts that have been confirmed by site-directed mutagenesis, while the phosphorylation of positions in the N or C terminal tails more than 10 amino acids away from the kinase domain do not involve important domain-domain contacts away from the substrate binding site.

This stimulates the kinase activity of EGFR, which leads to transautophosphorylation on multiple tyrosine residues in C-terminal end of the molecule.

[3] The Src-family kinases are examples of proteins that utilize autophosphorylation to sustain their activated states.

The activated ATM triggers a sequence of events including cell cycle arrest which allows time for the repair of the damaged DNA.

If damaged DNA is left unrepaired, it can lead to cell death or genomic instability, cancer and other pathologies.