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Novel redox-dependent regulation of NOX5 by the tyrosine kinase c-Abl.
Free Radic Biol Med 2008; 44(5):868-81FR

Abstract

We investigated the mechanism of H(2)O(2) activation of the Ca(2+)-regulated NADPH oxidase NOX5. H(2)O(2) induced a transient, dose-dependent increase in superoxide production in K562 cells expressing NOX5. Confocal studies demonstrated that the initial calcium influx generated by H(2)O(2) is amplified by a feedback mechanism involving NOX5-dependent superoxide production and H(2)O(2). H(2)O(2) NOX5 activation was inhibited by extracellular Ca(2+) chelators, a pharmacological inhibitor of c-Abl, and overexpression of kinase-dead c-Abl. Transfected kinase-active GFP-c-Abl colocalized with vesicular sites of superoxide production in a Ca(2+)-dependent manner. In contrast to H(2)O(2), the Ca(2+) ionophore ionomycin induced NOX5 activity independent of c-Abl. Immunoprecipitation of cell lysates revealed that active GFP-c-Abl formed oligomers with endogenous c-Abl and that phosphorylation of both proteins was increased by H(2)O(2) treatment. Furthermore, H(2)O(2)-induced NOX5 activity correlated with increased localization of c-Abl to the membrane fraction, and NOX5 proteins could be coimmunoprecipitated with GFP-Abl proteins. Our data demonstrate for the first time that NOX5 is activated by c-Abl through a Ca(2+)-mediated, redox-dependent signaling pathway and suggest a functional association between NOX5 NADPH oxidase and c-Abl.

Authors+Show Affiliations

Department of Medicine, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA. AkoulouzeBik@uthscsa.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18160052

Citation

El Jamali, Amina, et al. "Novel Redox-dependent Regulation of NOX5 By the Tyrosine Kinase C-Abl." Free Radical Biology & Medicine, vol. 44, no. 5, 2008, pp. 868-81.
El Jamali A, Valente AJ, Lechleiter JD, et al. Novel redox-dependent regulation of NOX5 by the tyrosine kinase c-Abl. Free Radic Biol Med. 2008;44(5):868-81.
El Jamali, A., Valente, A. J., Lechleiter, J. D., Gamez, M. J., Pearson, D. W., Nauseef, W. M., & Clark, R. A. (2008). Novel redox-dependent regulation of NOX5 by the tyrosine kinase c-Abl. Free Radical Biology & Medicine, 44(5), pp. 868-81.
El Jamali A, et al. Novel Redox-dependent Regulation of NOX5 By the Tyrosine Kinase C-Abl. Free Radic Biol Med. 2008 Mar 1;44(5):868-81. PubMed PMID: 18160052.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel redox-dependent regulation of NOX5 by the tyrosine kinase c-Abl. AU - El Jamali,Amina, AU - Valente,Anthony J, AU - Lechleiter,James D, AU - Gamez,Maria J, AU - Pearson,Doran W, AU - Nauseef,William M, AU - Clark,Robert A, Y1 - 2007/12/08/ PY - 2007/06/28/received PY - 2007/10/26/revised PY - 2007/11/19/accepted PY - 2007/12/28/pubmed PY - 2008/4/25/medline PY - 2007/12/28/entrez SP - 868 EP - 81 JF - Free radical biology & medicine JO - Free Radic. Biol. Med. VL - 44 IS - 5 N2 - We investigated the mechanism of H(2)O(2) activation of the Ca(2+)-regulated NADPH oxidase NOX5. H(2)O(2) induced a transient, dose-dependent increase in superoxide production in K562 cells expressing NOX5. Confocal studies demonstrated that the initial calcium influx generated by H(2)O(2) is amplified by a feedback mechanism involving NOX5-dependent superoxide production and H(2)O(2). H(2)O(2) NOX5 activation was inhibited by extracellular Ca(2+) chelators, a pharmacological inhibitor of c-Abl, and overexpression of kinase-dead c-Abl. Transfected kinase-active GFP-c-Abl colocalized with vesicular sites of superoxide production in a Ca(2+)-dependent manner. In contrast to H(2)O(2), the Ca(2+) ionophore ionomycin induced NOX5 activity independent of c-Abl. Immunoprecipitation of cell lysates revealed that active GFP-c-Abl formed oligomers with endogenous c-Abl and that phosphorylation of both proteins was increased by H(2)O(2) treatment. Furthermore, H(2)O(2)-induced NOX5 activity correlated with increased localization of c-Abl to the membrane fraction, and NOX5 proteins could be coimmunoprecipitated with GFP-Abl proteins. Our data demonstrate for the first time that NOX5 is activated by c-Abl through a Ca(2+)-mediated, redox-dependent signaling pathway and suggest a functional association between NOX5 NADPH oxidase and c-Abl. SN - 0891-5849 UR - https://www.unboundmedicine.com/medline/citation/18160052/Novel_redox_dependent_regulation_of_NOX5_by_the_tyrosine_kinase_c_Abl_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(07)00787-3 DB - PRIME DP - Unbound Medicine ER -