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Inhibition of protein tyrosine phosphatase non-receptor type 2 by PTP inhibitor XIX: Its role as a multiphosphatase inhibitor
Hien Thi Thu Le1, Young-Chang Cho1, Sayeon Cho1,*
1College of Pharmacy, Chung-Ang University
Protein tyrosine phosphatases (PTPs) play crucial roles in signal transduction and their functional alteration has been detected in many diseases. PTP inhibitors have been developed as therapeutic drugs for diseases that are related to the activity of PTPs. In this study, PTP inhibitor XIX, an inhibitor of CD45 and PTEN, was investigated whether it inhibits other PTPs. Protein tyrosine phosphatase non-receptor type 2 (PTPN2) was selectively inhibited by the inhibitor in a competitive manner. Drug affinity responsive target stability (DARTS) analysis showed that the inhibitor induces conformational changes in PTPN2. Phosphorylation levels of signal transducer and activator of transcription 3 (STAT3) at Tyr-705, a crucial site for STAT3 activation and target site of PTPN2, decreased upon exposure to the inhibitor. Our results suggest that PTP inhibitor XIX might be considered as an effective regulator of PTPN2 for treating diseases related to PTPN2.
Abstract, Accepted Manuscript(in press) [Submitted on January 5, 2017, Accepted on February 20, 2017]
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