Protein phosphorylation

Protein phosphorylation is a reversible post-translational modification of proteins in which an amino acid residue is phosphorylated by a protein kinase by the addition of a covalently bound phosphate group. Phosphorylation alters the structural conformation of a protein, causing it to become either activated or deactivated, or otherwise modifying its function. Approximately 13000 human proteins have sites that are phosphorylated. The reverse reaction of phosphorylation is called dephosphorylation, and is catalyzed by protein phosphatases. Protein kinases and phosphatases work independently and in a balance to regulate the function of proteins. The amino acids most commonly phosphorylated are serine, threonine, tyrosine in eukaryotes, and also histidine in prokaryotes and plants (though it is now known to be common in humans). These phosphorylations play important and well-characterized roles in signaling pathways and metabolism. However, other amino acids can also be phosphorylated post-translationally, including arginine, lysine, aspartic acid, glutamic acid and cysteine, and these phosphorylated amino acids have recently been identified to be present in human cell extracts and fixed human cells using a combination of antibody-based analysis (for pHis) and mass spectrometry (for all other amino acids). Protein phosphorylation was first reported in 1906 by Phoebus Levene at the Rockefeller Institute for Medical Research with the discovery of phosphorylated vitellin. However, it was nearly 50 years until the enzymatic phosphorylation of proteins by protein kinases was discovered. In 1906, Phoebus Levene at the Rockefeller Institute for Medical Research identified phosphate in the protein vitellin (phosvitin), and by 1933 had detected phosphoserine in casein, with Fritz Lipmann. However, it took another 20 years before Eugene P. Kennedy described the first ‘enzymatic phosphorylation of proteins’. The first phosphorylase enzyme was discovered by Carl and Gerty Cori in the late 1930s.