期刊
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
卷 526, 期 1, 页码 9-15出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2012.06.005
关键词
CaMKP/PPM1F; Disulfide-bond formation; Oxidation/reduction; PPM family; Protein phosphatase; ROS
Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP/PPM1F) is a Ser/Thr protein phosphatase that dephosphorylates and regulates multifunctional Ca2+/calmodulin-dependent protein kinases. Although CaMKP is known to be activated by phosphorylation with CaMKII and stimulated by the addition of polycations such as poly-L-lysine, detailed mechanisms of regulation of CaMKP in vivo still remain unclear. in the present study, we found that CaMKP is regulated by oxidation/reduction at Cys residue(s). When CaMKP was incubated with H2O2, time- and dose-dependent inactivation of the enzyme was observed. This inactivation was restored when the inactivated CaMKP was treated with a reducing agent such as 2-mercaptoethanol. Since there are three Cys residues (Cys-259, Cys-315, and Cys-359) in human CaMKP (hCaMKP), we produced three point mutants of hCaMKP, CaMKP(C259S), CaMKP(C315S), and CaMKP(C359S), of which the Cys residues were replaced by Set residues. Among these Cys-substituted mutants, only CaMKP(C359S) exhibited significant tolerance against oxidation by H2O2. Incubation of CaMKP with H2O2 led to formation of disulfide bond between Cys-359 and Cys-259/Cys-315, resulting in the inactivation of the enzyme. These results suggest that hCaMKP activity is reversibly regulated by oxidation/reduction at Cys-359. (C) 2012 Elsevier Inc. All rights reserved.
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