Effects of cations on ceramide-activated protein phosphatase 2A.
- Author:
Sehamuddin GALADARI
1
;
Abdulkadir HAGO
;
Mahendra PATEL
Author Information
1. Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al-Ain. sehamuddin@uaeu.ac.ae.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
cations;
ceramide;
phosphatases
- MeSH:
Cations, Divalent/*pharmacology;
Cell Line;
Edetic Acid/pharmacology;
Egtazic Acid/pharmacology;
Enzyme Activation;
Human;
Lymphocytes/cytology;
Phosphoprotein Phosphatase/drug effects/isolation & purification/*metabolism
- From:Experimental & Molecular Medicine
2001;33(4):240-244
- CountryRepublic of Korea
- Language:English
-
Abstract:
Characterization of ceramide-effector(s), which includes protein phosphatase 2A (PP2A) is an important prelude to understanding the molecular basis of sphingolipid-mediated biological effects such as cell growth, differentiation and apoptosis. Recently, the existence of a metal-dependent form of PP2A has been reported (Cai et al., 1995). In this study, we investigated the effects of metal ions and chelators on ceramide-activated PP2A (CAPP). Our study demonstrates that at 0.5 mM concentration, Mg2+ appears to have no significant effect on either basal or ceramide-stimulated phosphatase activities, whereas Ca2+ stimulated the basal phosphatase activity, but was inhibitory towards CAPP. Moreover, the divalent cations Cr2+, Mn2+, Fe2+, Ni2+, Cu2+ and Zn2+ were tested and all were found to be inhibitory towards both CAPP and basal phosphatase activities. By contrast, Cs+ and Li+ had almost no effect on CAPP, although both stimulated basal phosphatase activity. The effects of EDTA and EGTA were tested and it was observed that EDTA decreased CAPP activity in a dose-dependent fashion, but had no effect upon basal phosphatase activity. These results suggest that CAPP is a metal-dependent protein, but, because Ca2+ inhibitied CAPP and EGTA was much less potent than EDTA in inhibiting CAPP, Ca2+ is unlikely to be its metal cofactor.
