1. Interaction between the SH3 domains and C-terminal proline-rich region in NADPH oxidase organizer 1 (Noxo1).
- Author
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Yamamoto A, Kami K, Takeya R, and Sumimoto H
- Subjects
- Adaptor Proteins, Signal Transducing, Binding Sites, Cells, Cultured, Dose-Response Relationship, Drug, Humans, NADPH Oxidase 2, Neutrophils drug effects, Protein Binding, src Homology Domains physiology, Adaptor Proteins, Vesicular Transport metabolism, Arachidonic Acid administration & dosage, Membrane Glycoproteins metabolism, NADPH Oxidases metabolism, Neutrophils metabolism, Proline metabolism
- Abstract
NADPH oxidase organizer 1 (Noxo1), harboring a PX domain, two SH3 domains, and a proline-rich region (PRR), participates in activation of superoxide-producing Nox-family NADPH oxidases. Here, we show that Noxo1 supports superoxide production in a cell-free system for gp91(phox)/Nox2 activation by arachidonic acid. This lipid enhances an SH3-mediated binding of Noxo1 to p22(phox), a protein complexed with Nox oxidases; the binding is known to be required for Nox activation. We also demonstrate that the bis-SH3 domain directly interacts with the Noxo1 PRR. The interaction appears to prevent the bis-SH3 domain and PRR from binding to their target proteins; disruption of the intramolecular interaction facilitates Noxo1 binding to p22(phox) and also allows the PRR to associate with the Nox activator Noxa1, which association is crucial for Nox activation as well. These findings suggest that Nox activation involves a conformational change leading to disruption of the bis-SH3-PRR interaction in Noxo1.
- Published
- 2007
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