Crossphosphorylation

Crossphosphorylation is a term used to describe phosphorylation events in which a protein kinase transfers a phosphate group to a target protein, often another kinase or signaling effector, as part of a signaling cascade. It is commonly discussed in the context of transphosphorylation, where two kinase molecules in proximity phosphorylate each other or associated substrates, as opposed to autophosphorylation, in which a kinase phosphorylates itself.

In receptor tyrosine kinase signaling, crossphosphorylation typically occurs when ligand-induced dimerization brings kinase domains into proximity, enabling transphosphorylation on specific tyrosine residues. The resulting phosphate marks create docking sites for downstream signaling proteins and propagate the signal. Crossphosphorylation also features in other signaling architectures, such as two-component systems in bacteria, where a sensor kinase can relay a phosphate to a response regulator, and in cross-talk between kinases, where one kinase phosphorylates substrates that are not its canonical targets.

The significance of crossphosphorylation lies in its role in signal amplification, regulation, and specificity. Phosphorylation state changes can control protein conformation, interaction networks, and activity, allowing cells to fine-tune responses to stimuli. Experimental study typically involves in vitro kinase assays, phospho-specific antibodies, mass spectrometry, and mutational analyses to identify participating kinases and phosphorylation sites.

Overall, crossphosphorylation is a central mechanism by which signaling networks transmit and regulate information, enabling coordinated cellular responses.