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Sequential activation of phosphatidylinositol 3-kinase, βPix, Rac1, and Nox1 in growth factor-induced production of H2O2
- Sequential activation of phosphatidylinositol 3-kinase, βPix, Rac1, and Nox1 in growth factor-induced production of H2O2
- Hye S.P.; Seung H.L.; Park D.; Jun S.L.; Sung H.R.; Won J.L.; Sue G.R.; Yun S.B.
- Ewha Authors
- 이서구; 배윤수; 이원재
- SCOPUS Author ID
- 이서구; 배윤수
- Issue Date
- Journal Title
- Molecular and Cellular Biology
- Molecular and Cellular Biology vol. 24, no. 10, pp. 4384 - 4394
- SCI; SCIE; SCOPUS
- Document Type
- 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 gp91phox (Nox2) of phagocytic cells, is constitutively associated with βPix, a guanine nucleotide exchange factor for Rac. Both growth factor-induced ROS production and Rac1 activation were completely blocked in cells depleted of βPix 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, βPix, and Rac1, which then binds to Nox1 to stimulate its NADPH oxidase activity. Copyright © 2004, American Society for Microbiology. All Rights Reserved.
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