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Protein phosphorylation is a 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 activated, deactivated, or modifying its function. 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, and tyrosine in eukaryotes, and histidine in prokaryotes, which play important and well-characterized roles in signaling pathways and metabolism. However, many other amino acids can also be phosphorylated, including arginine, lysine, and cysteine. 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. ==Functions of phosphorylation== Phosphorylation introduces a charged and hydrophilic segment at the R group of the modified amino acid, changing a protein's structure by altering interactions with nearby amino acids. Some proteins such as p53 contain multiple phosphorylation sites, facilitating complex, multi-level regulation. Because of the ease with which proteins can be phosphorylated and dephosphorylated, this type of modification is a flexible mechanism for cells to respond to external signals and environmental conditions.〔Johnson L N, Barford D. The effects of phosphorylation on the structure and function of proteins(). Annual review of biophysics and biomolecular structure, 1993, 22(1): 199-232.〕 The first example of protein regulation by phosphorylation was glycogen phosphorylase. Eddie Fisher and Ed Krebs described how phosphorylation of glycogen phosphorylase ''b'' converted it to the active glycogen phosphorylase ''a''. It was soon discovered that glycogen synthase, another metabolic enzyme, is inactivated by phosphorylation. Regulatory roles of phosphorylation include: *Biological thermodynamics of energy-requiring reactions * *Phosphorylation of Na+/K+-ATPase during the transport of sodium (Na+) and potassium (K+) ions across the cell membrane in osmoregulation to maintain homeostasis of the body's water content. *Mediates enzyme inhibition * *Phosphorylation of the enzyme GSK-3 by AKT (Protein kinase B) as part of the insulin signaling pathway. * *Phosphorylation of src tyrosine kinase (pronounced "sarc") by C-terminal Src kinase (Csk) induces a conformational change in the enzyme, resulting in a fold in the structure, which masks its kinase domain, and is thus shut "off". * Important for protein-protein interaction via "recognition domains." * *Phosphorylation of the cytosolic components of NADPH oxidase, a large membrane-bound, multi-protein enzyme present in phagocytic cells, plays an important role in the regulation of protein-protein interactions in the enzyme. * Important in protein degradation. * *In the late 1990s, it was recognized that phosphorylation of some proteins causes them to be degraded by the ATP-dependent ubiquitin/proteasome pathway. These target proteins become substrates for particular E3 ubiquitin ligases only when they are phosphorylated. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Protein phosphorylation」の詳細全文を読む スポンサード リンク
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