Inhibition of DUSP13B Activity by NSC 663284

摘要

Dual-specificity phosphatases (DUSPs) are group of enzymes that belong to the superfamily of protein-tyrosine phosphatases and catalyze dephosphorylation of proteins at both phosphorylated tyrosine and serine/threonine residues. Several members of the DUSP family have distinct substrate specificity, subcellular localization, and induced expression pattern by extracellular stimuli.3 These phosphatases play an important role in the regulation of intracellular signaling cascades governing cell growth, differentiation, and apoptosis. Among several phosphatases, DUSP 13 encodes two distinct DUSPs in alternative reading frames, called MDSP (muscle-restricted DUSP) and TMDP (testis- and skeletal muscle-specific DUSP). They are called DUSP13A and DUSP13B, respectively. DUSP13 can dephosphorylate phosphotyrosine and phosphoserine/ threonine residues, but cellular targets of DUSP 13 proteins are yet to be characterized. Our recent report showed that DUSP13A interacts with and activates apoptosis signal-regulating kinase 1 (ASK1) regardless of its phosphatase activity. DUSP13B is up-regulated at the meiotic stage and expressed stage-specifically during spermatogenesis. According to the study of Katagiri et ah, contrary to DUSP 13A, DUSP13B inactivates mitogen-activated protein kinase (MAPK) activation in the order of selectivity, JNK = p38 >ERK in cells, while DUSP13A did not show MAPK phosphatase activity.