Phosphorylation is the addition of a
phosphate (PO
4) group to a
protein or other organic molecule. Protein phosphorylation in particular plays a significant role in a wide range of cellular processes. Its prominent role in
biochemistry is the subject of a very large body of research (as of February 2008, the
Medline database returns nearly 148,000 articles on the subject, largely on
protein phosphorylation).
In 1906, Phoebus A. Levene at the Rockefeller Institute for Medical Research identified phosphate in the protein Vitellin (phosvitin),[1] and by 1933 had detected phosphoserine in Casein, with Fritz Lipmann.[2] However, it took another 20 years before Eugene P. Kennedy described the first ‘enzymatic phosphorylation of proteins’.[3]
Reversible phosphorylation of proteins is an important regulatory mechanism that occurs in both prokaryotic and eukaryotic organisms.[4][5][6][7] Enzymes called kinases (phosphorylation) and phosphatases (dephosphorylation) are involved in this process. Many enzymes and receptors are switched "on" or "off" by phosphorylation and dephosphorylation. Reversible phosphorylation results in a conformational change in the structure in many enzymes and receptors, causing them to become activated or deactivated. Phosphorylation usually occurs on serine, threonine, and tyrosine residues in eukaryotic proteins. In addition, phosphorylation occurs on the basic amino acid residues histidine or arginine or lysine in prokaryotic proteins[4][5]. The addition of a phosphate (PO4) molecule to a polar R group of an amino acid residue can turn a hydrophobic portion of a protein into a polar and extremely hydrophilic portion of molecule. In this way it can introduce a conformational change in the structure of the protein via interaction with other hydrophobic and hydrophilic residues in the protein.
One such example of the regulatory role that phosphorylation plays is the p53 tumor suppressor protein. The p53 protein is heavily regulated[8] and contains more than 18 different phosphorylation sites. Activation of p53 can lead to cell cycle arrest, which can be reversed under some circumstances, or apoptotic cell death[9] This activity occurs only in situations wherein the cell is damaged or physiology is disturbed in normal healthy individuals.
