This research was supported by a Crizotinib buy Grant-in-Aid for Research Program on Innovative Technologies for Animal Breeding, Reproduction, and Vaccine Development (REP-1002) from the Ministry of Agriculture, Forestry and Fisheries of Japan and a Grant-in-Aid for Scientific Research (No.24380155) from the Japan Society for the Promotion of Science (JSPS).
Phosphorylation of proteins is one of the most important means of regulating signaling events required for basic cellular function. Phosphorylation is reversible and often induces a conformational change that affects the enzymatic activity or scaffolding function of the protein. This in turn affects the propagation of signals in the cell, thus leading to either enhancement or suppression of cellular processes.

Changes in protein phosphorylation are controlled by a wide array of protein kinases and phosphatases. Among the protein phosphatases, protein tyrosine phosphatases (PTPs), comprise the largest family. Although these enzymes exhibit widely diverse sequences and structures, they all contain the C(X)5R amino acid sequence in their catalytic cleft (Guan and Dixon, 1990). The invariant cysteine residue in this motif is responsible for the catalytic activity of the enzyme, and substitution of the cysteine for a serine residue abrogates activity (Streuli et al., 1989; Guan and Dixon, 1990; Guan et al., 1991). Within the PTP family, the dual-specificity phosphatases are unique in their ability to catalyze the dephosphorylation of phosphoserine and phosphothreonine residues in addition to phosphotyrosine residues (Guan et al.

, 1991; Charles et al., 1992; Alessi et al., 1993; Patterson et al., 2009). Notably, the tumor suppressor protein PTEN (phosphatase and tensin homolog deleted on chromosome 10), a nontypical member of the dual-specificity PTP family, catalyzes the dephosphorylation of phosphatidylinositides (Myers et al., 1997; Carfilzomib Maehama and Dixon, 1998). A screen for new dual-specificity phosphatases based on the sequence of the catalytic motif of PTEN resulted in the discovery of PTP localized to mitochondrion 1 (PTPMT1) (Pagliarini et al., 2004). PTPMT1 enjoys the distinction of being among the first protein phosphatases found to localize primarily to mitochondria, where it resides on the inner membrane facing the mitochondrial matrix (Pagliarini et al., 2005). Interestingly, PTPMT1 has been identified in pancreatic islets (Pagliarini et al., 2005). In the ��-cell, the sole insulin-producing cell in the body, knockdown of expression of PTPMT1 resulted in a dramatic increase of cellular ATP levels and insulin secretion (Pagliarini et al., 2005), suggesting that PTPMT1 may be a potential target in the ��-cell for the treatment of type II diabetes.