title: Inhibition of protein tyrosine phosphatase non-receptor type 2 by PTP inhibitor XIX: Its role as a multiphosphatase inhibitor.
abstract: 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. [BMB Reports 2017; 50(6): 329-334].
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul 06974, Korea.
authors.forename: Hien Thi Thu
authors.initials: HTT
authors.lastname: Le
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul 06974, Korea.
authors.forename: Young-Chang
authors.initials: YC
authors.lastname: Cho
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul 06974, Korea.
authors.forename: Sayeon
authors.initials: S
authors.lastname: Cho
mesh_terms: D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D010766:Phosphorylation / Q000235:genetics / Q000502:physiology; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000235:genetics / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D050796:STAT3 Transcription Factor; D017493:Leukocyte Common Antigens; C516649:PTPN2 protein, human; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2; D017027:Protein Tyrosine Phosphatases