Abstract
It is well established that growth-factor-induced reactive oxygen species (ROS) act as second messengers in cell signaling. We have previously reported that βPix, a guanine nucleotide exchange factor for Rac, interacts with NADPH oxidase 1 (Nox1) leading to EGF-induced ROS generation. Here, we report the identification of the domains of Nox1 and βPix responsible for the interaction between the two proteins. GST pull-down assays show that the PH domain of βPix binds to the FAD-binding region of Nox1. We also show that overexpression of the PH domain of βPix results in inhibition of superoxide anion generation in response to EGF. Additionally, NADPH oxidase Organizer 1 (NoxO1) is shown to interact with the NADPH-binding region of Nox1. These results suggest that the formation of the complex consisting of Nox1, βPix, and NoxO1 is likely to be a critical step in EGF-induced ROS generation.
Original language | English |
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Pages (from-to) | 985-990 |
Number of pages | 6 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 339 |
Issue number | 3 |
DOIs | |
State | Published - 20 Jan 2006 |
Bibliographical note
Funding Information:We thank Dr. Sumimoto for the plasmid DNA (pEF-Bos-NoxO1 and pEF-Bos-NoxA1) and Dr. Leto for the retrovirus encoding Nox1. We thank Dr. Jaesang Kim for critical reading. This work is supported by the Korea Science and Engineering Foundation (KOSEF) through the Center for Cell Signaling Research at Ewha Womans University, by 21st Century Frontier Functional Proteomics Project (FPR05C2-510), and by Grant M103KV010013-04K2201-01310 to D.P. from Brain Research Center of the 21st Century Frontier Research Program from the Ministry of Science and Technology. H.S.P. is the recipient of BK21 scholarship and of KRF-2005-216-C00126 from Korea Research Foundation.
Keywords
- EGF
- NADPH oxidase 1
- NADPH oxidase Organizer 1
- Reactive oxygen species
- Superoxide anion
- βPix