Regulation of the NADPH-oxidase complex of phagocytic leukocytes. Recent insights from structural biology, molecular genetics, and microscopy

Histochemistry and Cell Biology
John M RobinsonJohn A Badwey

Abstract

The NADPH-oxidase complex is a multisubunit enzyme complex that catalyzes the formation of superoxide (O2-) by phagocytic leukocytes. This paper reviews some of the major advances in understanding the assembly and regulation of this enzyme system that have occurred during the past decade. For example, novel domains/motifs have been identified in p47-phox (PX and super SH3 domains) and p67-phox (tetratricopeptide repeat motifs). X-ray crystallography and NMR spectroscopy have provided detailed structural data on these domains and how p47-phox and p67-phox interact with p22-phox and activated Rac, respectively. Site-directed mutagenesis and knockout experiments have identified the critical phosphorylation sites in p47-phox, revealed an "activation domain" in p67-phox, and demonstrated that a specific pathway exists for activating Rac to participate in oxidase assembly/activation. Cytochemistry and immunofluorescence microscopy have provided new insights into the assembly of the oxidase and reveal a level of complexity not previously appreciated.

References

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Citations

Dec 23, 2004·Histochemistry and Cell Biology·Esther Asan, Detlev Drenckhahn
Nov 1, 2007·Histochemistry and Cell Biology·Christian ZuberJürgen Roth
Jul 4, 2008·Histochemistry and Cell Biology·John M Robinson
Feb 19, 2009·Histochemistry and Cell Biology·John M Robinson
Sep 22, 2006·Antioxidants & Redox Signaling·Henk-Jan van ManenCees Otto
Sep 22, 2006·Antioxidants & Redox Signaling·Janet V Cross, Dennis J Templeton
Sep 8, 2007·Antioxidants & Redox Signaling·Louisa Papatheodorou, Norbert Weiss
Jun 20, 2006·Molecular and Cellular Biology·Caroline MartyRichard D Ye
Jan 13, 2010·Journal of Translational Medicine·Ekua W BrenuSonya M Marshall-Gradisnik
Apr 9, 2008·Journal of Leukocyte Biology·Kazuhiro OmoriThomas E Van Dyke
Jul 19, 2006·Canadian Journal of Physiology and Pharmacology·Kathy K W Au-YeungKarmin O
Jul 17, 2009·Pharmacological Reports : PR·Krzysztof BryniarskiWłodzimierz Ptak
Jan 23, 2009·Advances in Enzyme Regulation·Martin Klemke, Yvonne Samstag
Jul 16, 2008·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Grace YuDavid B Lewis
Feb 27, 2008·Seminars in Cell & Developmental Biology·Roland Wedlich-Soldner, Rong Li
Nov 26, 2013·International Reviews of Immunology·Armando RojasIsrael Rojas
Dec 4, 2013·Thrombosis Research·Eduardo FuentesIván Palomo
Dec 7, 2006·Histochemistry and Cell Biology·Douglas J TaatjesJürgen Roth
Nov 12, 2005·Histochemistry and Cell Biology·Douglas J Taatjes, Jürgen Roth
Jan 24, 2007·Physiological Reviews·Karen Bedard, Karl-Heinz Krause
Feb 14, 2017·Genes & Cancer·Noushin NabaviLuciano Mutti
Nov 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Robert GyurkoThomas E Van Dyke

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