Regulation of Annexin A2 by Reversible Glutathionylation
| Autor: | David M. Waisman, Nolan R. Filipenko, Jennifer F. Caplan, Sandra L. Fitzpatrick |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Protein subunit
Biochemistry Mass Spectrometry Dithiothreitol Structure-Activity Relationship chemistry.chemical_compound Annexin Glutaredoxin Animals Homeostasis Biotinylation Cysteine Molecular Biology Annexin A2 Glutaredoxins Phospholipids Diamide biology Tumor Necrosis Factor-alpha S100A10 Proteins Hydrogen Peroxide Cell Biology Glutathione Oxidants Heterotetramer Actins Oxidative Stress chemistry Liposomes biology.protein Cattle Oxidoreductases Oxidation-Reduction |
| Zdroj: | Journal of Biological Chemistry. 279:7740-7750 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m313049200 |
| Popis: | The annexin A2-S100A10 heterotetramer (AIIt) is a multifunctional Ca(2+)-dependent, phospholipid-binding, and F-actin-binding phosphoprotein composed of two annexin A2 subunits and two S100A10 subunits. It was reported previously that oxidative stress from exogenous hydrogen peroxide or generated in response to tumor necrosis factor-alpha results in the glutathionylation of Cys(8) of annexin A2. In this study, we demonstrate that AIIt is an oxidatively labile protein whose level of activity is regulated by the redox status of its sulfhydryl groups. Oxidation of AIIt by diamide resulted in a time- and concentration-dependent loss of the ability of AIIt to interact with phospholipid liposomes and F-actin. The inhibitory effect of diamide on the activity of AIIt was partially reversed by dithiothreitol. In addition, incubation of AIIt with diamide and GSH resulted in the glutathionylation of AIIt in vitro. Mass spectrometry established the incorporation of 2 mol of GSH/mol of annexin A2 subunit at Cys(8) and Cys(132). Glutathionylation potentiated the inhibitory effects of diamide on the activity of AIIt. Furthermore, AIIt could be deglutathionylated by glutaredoxin (thiol transferase). Thus, we show for the first time that AIIt can undergo functional reactivation by glutaredoxin, therefore establishing that AIIt is regulated by reversible glutathionylation. |
| Databáze: | OpenAIRE |
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