NDLI: Activation of Dual Oxidases Duox1 and Duox2

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Activation of Dual Oxidases Duox1 and Duox2

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Communi, David Hoste, Candice Corvilain, Bernard Grasberger, Helmut Milenkovic, Milutin De Deken, Xavier Dumont, Jacques E. Rigutto, Sabrina Miot, Françoise
Description	Author Affiliation: Rigutto S ( Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre Bruxelles, Brussels, Belgium. sabrina.rigutto@ulb.ac.be)
Abstract	Dual oxidases were initially identified as NADPH oxidases producing $H_{2}O_{2}$ necessary for thyroid hormone biosynthesis. The crucial role of Duox2 has been demonstrated in patients suffering from partial iodide organification defect caused by bi-allelic mutations in the DUOX2 gene. However, the Duox1 function in thyroid remains elusive. We optimized a functional assay by co-expressing Duox1 or Duox2 with their respective maturation factors, DuoxA1 and DuoxA2, to compare their intrinsic enzymatic activities under stimulation of the major signaling pathways active in the thyroid in relation to their membrane expression. We showed that basal activity of both Duox isoenzymes depends on calcium and functional EF-hand motifs. However, the two oxidases are differentially regulated by activation of intracellular signaling cascades. Duox1 but not Duox2 activity is stimulated by forskolin $(EC_{50}$ = 0.1 μm) via protein kinase A-mediated Duox1 phosphorylation on serine 955. In contrast, phorbol esters induce Duox2 phosphorylation via protein kinase C activation associated with high $H_{2}O_{2}$ generation (phorbol 12-myristate 13-acetate $EC_{50}$ = 0.8 nm). These results were confirmed in human thyroid cells, suggesting that Duox1 is also involved in thyroid hormonogenesis. Our data provide, for the first time, detailed insights into the mechanisms controlling the activation of Duox1–2 proteins and reveal additional phosphorylation-mediated regulation.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	11
Volume Number	284
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2009-03-13
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cell Membrane Enzymology Cyclic AMP-Dependent Protein Kinases Metabolism NADPH Oxidase Protein Kinase C Thyroid Gland Animals COS Cells Carcinogens Pharmacology Genetics Cercopithecus Aethiops Colforsin Enzyme Activation Drug Effects Physiology Hydrogen Peroxide Iodides Membrane Proteins Mutation Phosphorylation Signal Transduction Tetradecanoylphorbol Acetate Thyroid Diseases Thyroid Hormones Biosynthesis Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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