Park Hye Sun, Lee Seung Hye, Park Dongeun, Lee Jun Sung, Ryu Sung Ho, Lee Won Jae, Rhee Sue Goo, Bae Yun Soo
Center for Cell Signaling Research, Division of Molecular Life Sciences, Ewha Womans University, Seoul 120-750, Korea.
Mol Cell Biol. 2004 May;24(10):4384-94. doi: 10.1128/MCB.24.10.4384-4394.2004.
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.
在生长因子刺激的细胞中，活性氧（ROS）的产生需要磷脂酰肌醇3激酶（PI3K）和Rac蛋白的激活。我们在此报告，Nox1的COOH末端区域（一种与吞噬细胞的gp91(phox)（Nox2）相关的蛋白质）与Rac的鸟嘌呤核苷酸交换因子βPix组成性结合。通过RNA干扰使βPix缺失的细胞中，生长因子诱导的ROS产生和Rac1激活均被完全阻断。Rac1还被证明以生长因子依赖的方式与Nox1的COOH末端区域结合。此外，RNA干扰使Nox1缺失抑制了生长因子诱导的ROS生成。这些结果表明，生长因子刺激的细胞中ROS的产生是由PI3K、βPix和Rac1的顺序激活介导的，然后Rac1与Nox1结合以刺激其NADPH氧化酶活性。
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