PTP inhibitor IV protects JNK kinase activity by inhibiting dual-specificity phosphatase 14 (DUSP14).
Protein phosphorylation plays critical roles in the regulation of protein activity and cell signaling. The level of protein phosphorylation is controlled by protein kinases and protein tyrosine phosphatases (PTPs). Disturbance of the equilibrium between protein kinase and PTP activities results in abnormal protein phosphorylation, which has been linked to the etiology of several diseases, including cancer. In this study, we screened protein tyrosine phosphatases (PTPs) by in vitro phosphatase assays to identify PTPs that are inhibited by bis (4-trifluoromethyl-sulfonamidophenyl, TFMS)-1,4-diisopropylbenzene (PTP inhibitor IV). PTP inhibitor IV inhibited DUSP14 phosphatase activity. Kinetic studies with PTP inhibitor IV and DUSP14 revealed a competitive inhibition, suggesting that PTP inhibitor IV binds to the catalytic site of DUSP14. PTP inhibitor IV effectively and specifically inhibited DUSP14-mediated dephosphorylation of JNK, a member of the mitogen-activated protein kinase (MAPK) family.
Park
Jae Eun
JE
Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejon, Republic of Korea.
Park
Byoung Chul
BC
Song
Mina
M
Park
Sung Goo
SG
Lee
Do Hee
DH
Park
So-Young
SY
Kim
Jae Hoon
JH
Cho
Sayeon
S
D002460:Cell Line; D054637:Dual-Specificity Phosphatases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D013449:Sulfonamides; C543088:bis(4-trifluoromethyl-sulfonamidophenyl)-1,4-diisopropyl-benzene; D048670:MAP Kinase Kinase 4; D054639:Mitogen-Activated Protein Kinase Phosphatases; C498843:DUSP14 protein, human; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases