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PTPN1
Tyrosine-protein phosphatase non-receptor type 1 also known as protein-tyrosine phosphatase 1B (PTP1B) is an enzyme that is the founding member of the protein tyrosine phosphatase (PTP) family. In humans it is encoded by the ''PTPN1'' gene.〔 PTP1B is a negative regulator of the insulin signaling pathway and is considered a promising potential therapeutic target, in particular for treatment of type 2 diabetes.〔 It has also been implicated in the development of breast cancer and has been explored as a potential therapeutic target in that avenue as well.〔〔〔
== Structure and function ==
PTP1B was first isolated from a human placental protein extract,〔〔 but it is expressed in many tissues.〔 PTP1B is localized to the cytoplasmic face of the endoplasmic reticulum.〔 PTP1B can dephosphorylate the phosphotyrosine residues of the activated insulin receptor kinase.〔〔〔 In mice, genetic ablation of PTPN1 results in enhanced insulin sensitivity.〔〔 Several other tyrosine kinases, including epidermal growth factor receptor,〔 insulin-like growth factor 1 receptor,〔 colony stimulating factor 1 receptor,〔 c-Src,〔 Janus kinase 2,〔 TYK2,〔 and focal adhesion kinase〔 as well as other tyrosine-phosphorylated proteins, including BCAR1,〔 DOK1,〔 beta-catenin〔 and cortactin〔 have also been described as PTP1B substrates.
The first crystal structure of the PTP1B catalytic domain revealed that the catalytic site exists within a deep cleft of the protein formed by three loops including the WPD loop with the Asp181 residue, a pTyr loop with the Tyr46 residue and a Q loop with the Gln262 residue.〔〔 The pTyr loop and Tyr46 residue are located on the surface of the protein, and thus help to determine the depth a substrate can obtain within the cleft. This acts as a means of driving selectivity, as substrates containing smaller phosphoresidues cannot reach the site of catalytic activity at the base of the cleft.〔 Upon substrate binding, PTP1B undergoes a structural modification in which the WPD loop closes around the substrate, introducing stabilizing pi stacking interactions between the aromatic rings of the phosphotyrosine (pTyr) substrate residue and the Phe182 residue on the WPD loop.〔
抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』
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