Phosphorylation is the addition of a phosphate (PO₄) group to a protein or a small molecule. Its prominent role in biochemistry is the subject of a very large body of research (the Medline database returns over 100,000 articles on the subject, largely on protein phosphorylation).

Protein phosphorylation

Function

In eukaryotes, protein phosphorylation is probably the most important regulatory event. Many enzymes and receptors are switched "on" or "off" by phosphorylation and dephosphorylation. Phosphorylation is catalyzed by various specific protein kinases, whereas phosphatases dephosphorylate.

An example of the important role that phosphorylation plays is the p53 tumor suppressor gene, which—when active—stimulates transcription of gene that suppress the cell cycle, even to the extent that it undergoes apoptosis. However, this activity should be limited to situations where the cell is damaged or physiology is disturbed. To this end, the p53 protein is extensively regulated. In fact, p53 contains more than 18 different phosphorylation sites.

Upon the deactivating signal, the protein becomes dephosphorylated again and stops working. This is the mechanism in many forms of signal transduction, for example the way in which incoming light is processed in the light-sensitive cells of the retina.

Signaling networks

The network underlying phosphorylation can be very complex. In some cellular signalling pathways, a protein A phosphorylates B, and B phosphorylates C, but A also phosphorylates C directly, and B can phosphorylate D, which may in turn phosphorylate A.

Types of phosphorylation

See also protein kinase for more details on the different types of phosphorylation

Within a protein, phosphorylation can occur on several amino acids. Phosphorylation on serine is the most common, followed by threonine. Tyrosine phosphorylation is relatively rare. However, since tyrosine phosphorylated proteins are relatively easy to purify using antibodies, tyrosine phosphorylation sites are relatively well understood. Histidine and aspartate phosphorylation occurs in prokaryotes as part of two-component signalling.

Other kinds

ATP, the "high-energy" exchange medium in the cell, is synthesized in the mitochondrion by addition of a third phosphate group to ADP in a process referred to as oxidative phosphorylation. ATP is also synthesized by substrate level phosphorylation during glycolysis. ATP is synthesized at the expense of solar energy by photophosphorylation in the chloroplasts of plant cells.

Phosphorylation of sugars is often the stage of their catabolism. It allows cells to accumulate sugars because the phosphate group prevents the molecules from diffusing back across their transporter.