title: Sequential activation of phosphatidylinositol 3-kinase, beta Pix, Rac1, and Nox1 in growth factor-induced production of H2O2.
abstract: The generation of reactive oxygen species (ROS) in cells stimulated with growth factors requires the activation of phosphatidylinositol 3-kinase (PI3K) and the Rac protein. We report here that the COOH-terminal region of Nox1, a protein related to gp91(phox) (Nox2) of phagocytic cells, is constitutively associated with beta Pix, a guanine nucleotide exchange factor for Rac. Both growth factor-induced ROS production and Rac1 activation were completely blocked in cells depleted of beta Pix by RNA interference. Rac1 was also shown to bind to the COOH-terminal region of Nox1 in a growth factor-dependent manner. Moreover, the depletion of Nox1 by RNA interference inhibited growth factor-induced ROS generation. These results suggest that ROS production in growth factor-stimulated cells is mediated by the sequential activation of PI3K, beta Pix, and Rac1, which then binds to Nox1 to stimulate its NADPH oxidase activity.
authors.affiliation: Center for Cell Signaling Research, Division of Molecular Life Sciences, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Hye Sun
authors.initials: HS
authors.lastname: Park
authors.forename: Seung Hye
authors.initials: SH
authors.lastname: Lee
authors.forename: Dongeun
authors.initials: D
authors.lastname: Park
authors.forename: Jun Sung
authors.initials: JS
authors.lastname: Lee
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Ryu
authors.forename: Won Jae
authors.initials: WJ
authors.lastname: Lee
authors.forename: Sue Goo
authors.initials: SG
authors.lastname: Rhee
authors.forename: Yun Soo
authors.initials: YS
authors.lastname: Bae
mesh_terms: D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D018938:Caco-2 Cells; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D009154:Mutation; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D064067:Rho Guanine Nucleotide Exchange Factors; D014162:Transfection; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C576606:ARHGEF7 protein, human; D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D064067:Rho Guanine Nucleotide Exchange Factors; D004815:Epidermal Growth Factor; D006861:Hydrogen Peroxide; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C402799:NOX1 protein, human; D019869:Phosphatidylinositol 3-Kinases; D020830:rac1 GTP-Binding Protein