{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:08:11Z","timestamp":1782990491470,"version":"3.54.5"},"reference-count":71,"publisher":"Rockefeller University Press","issue":"8","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,8,7]]},"abstract":"<jats:p>Superoxide produced by the phagocyte reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is essential for host defense. Enzyme activation requires translocation of p67phox, p47phox, and Rac-GTP to flavocytochrome b558 in phagocyte membranes. To examine the regulation of phagocytosis-induced superoxide production, flavocytochrome b558, p47phox, p67phox, and the Fc\u03b3IIA receptor were expressed from stable transgenes in COS7 cells. The resulting COSphoxFc\u03b3R cells produce high levels of superoxide when stimulated with phorbol ester and efficiently ingest immunoglobulin (Ig)G-coated erythrocytes, but phagocytosis did not activate the NADPH oxidase. COS7 cells lack p40phox, whose role in the NADPH oxidase is poorly understood. p40phox contains SH3 and phagocyte oxidase and Bem1p (PB1) domains that can mediate binding to p47phox and p67phox, respectively, along with a PX domain that binds to phosphatidylinositol-3-phosphate (PI(3)P), which is generated in phagosomal membranes. Expression of p40phox was sufficient to activate superoxide production in COSphoxFc\u03b3R phagosomes. Fc\u03b3IIA-stimulated NADPH oxidase activity was abrogated by point mutations in p40phox that disrupt PI(3)P binding, or by simultaneous mutations in the SH3 and PB1 domains. Consistent with an essential role for PI(3)P in regulating the oxidase complex, phagosome NADPH oxidase activation in primary macrophages ingesting IgG-coated beads was inhibited by phosphatidylinositol 3 kinase inhibitors to a much greater extent than phagocytosis itself. Hence, this study identifies a role for p40phox and PI(3)P in coupling Fc\u03b3R-mediated phagocytosis to activation of the NADPH oxidase.<\/jats:p>","DOI":"10.1084\/jem.20052085","type":"journal-article","created":{"date-parts":[[2006,8,2]],"date-time":"2006-08-02T07:47:53Z","timestamp":1154504873000},"page":"1915-1925","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":117,"title":["The phosphoinositide-binding protein p40<i>phox<\/i> activates the NADPH oxidase during Fc\u03b3IIA receptor\u2013induced phagocytosis"],"prefix":"10.1084","volume":"203","author":[{"given":"Chang-Il","family":"Suh","sequence":"first","affiliation":[{"name":"1Department of Pediatrics (Hematology\/Oncology), Herman B Wells Center for Pediatric Research, Riley Hospital for Children"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie D.","family":"Stull","sequence":"additional","affiliation":[{"name":"1Department of Pediatrics (Hematology\/Oncology), Herman B Wells Center for Pediatric Research, Riley Hospital for Children"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing Jun","family":"Li","sequence":"additional","affiliation":[{"name":"1Department of Pediatrics (Hematology\/Oncology), Herman B Wells Center for Pediatric Research, Riley Hospital for Children"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Tian","sequence":"additional","affiliation":[{"name":"1Department of Pediatrics (Hematology\/Oncology), Herman B Wells Center for Pediatric Research, Riley Hospital for Children"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne O.","family":"Price","sequence":"additional","affiliation":[{"name":"1Department of Pediatrics (Hematology\/Oncology), Herman B Wells Center for Pediatric Research, Riley Hospital for Children"},{"name":"3Department of Medical and Molecular Genetics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Grinstein","sequence":"additional","affiliation":[{"name":"5Division of Cell Biology, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Yaffe","sequence":"additional","affiliation":[{"name":"6Department of Biology, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Atkinson","sequence":"additional","affiliation":[{"name":"4Department of Medicine (Nephrology), Indiana University School of Medicine, Indianapolis, IN 46202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary C.","family":"Dinauer","sequence":"additional","affiliation":[{"name":"1Department of Pediatrics (Hematology\/Oncology), Herman B Wells Center for Pediatric Research, Riley Hospital for Children"},{"name":"2Department of Microbiology\/Immunology"},{"name":"3Department of Medical and Molecular Genetics,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2006,7,31]]},"reference":[{"key":"2023072515105322100_BIB1","year":"2003"},{"key":"2023072515105322100_BIB2","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1189\/jlb.0404216","volume":"76","year":"2004","journal-title":"J. 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