Kinases are enzymes that catalyze the addition of phosphoryl groups to certain amino acid residues on target molecules, which is called phosphorylation. To do this, a kinase will bind to ATP, hydrolyze the gamma (γ) phosphoryl, and bind to its target molecule, generating ADP in the process. Then, it transfers the phosphoryl group to the target molecule, dissociates, binds to a new ATP molecule. This process can then be repeated.


Phosphorylation Targets

Proteins make up the majority of target molecules that can be phosphorylated by kinases, but lipids (e.g. Phosphatidylinositol-4,5-bisphosphate 3, or PI3) can also be phosphorylated. On proteins, three major amino acid residues serve as major sites of phosphorylation: Tyrosines (Tyr, Y) Serines (Ser, S), and Threonines (Thr, T). They all possess a hydroxyl (-OH) group in their variable chain that can serve as a placement site for a phosphate group by kinases:



Phosphatases work in reverse to kinases, and are responsible for removing phosphate groups from their targets. Dephosphorylation that is catalyzed by phosphatases is important for maintaining homeostatic balance in the biological system – once a protein is phosphorylated for activation, it must be turned off via dephosphorylation by phosphatases or by protein degradation. Constitutively active phosphorylation signal pathways are hallmarks of numerous malignancies, including cancer.