Sequential activation of phosphatidylinositol 3-kinase, βPix, Rac1, and Nox1 in growth factor-induced production of H2O2

Sun Park Hye, Hye Lee Seung, Dongeun Park, Sung Lee Jun, Ho Ryu Sung, Jae Lee Won, Goo Rhee Sue, Soo Bae Yun

Research output: Contribution to journalArticlepeer-review

199 Scopus citations

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 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.

Original languageEnglish
Pages (from-to)4384-4394
Number of pages11
JournalMolecular and Cellular Biology
Volume24
Issue number10
DOIs
StatePublished - May 2004

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