The Rac Effector p67 phox Regulates Phagocyte NADPH Oxidase by Stimulating Vav1 Guanine Nucleotide Exchange Activity-Reference-Cited by-同舟云学术

The Rac Effector p67 phox Regulates Phagocyte NADPH Oxidase by Stimulating Vav1 Guanine Nucleotide Exchange Activity

Published:2007-01 Issue:1 Volume:27 Page:312-323
ISSN:0270-7306
Container-title:Molecular and Cellular Biology
language:en
Short-container-title:Mol Cell Biol

Author:

Ming Wenyu¹,Li Shijun¹,Billadeau Daniel D.²,Quilliam Lawrence A.³,Dinauer Mary C.¹⁴

Affiliation:

1. Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, 1044 West Walnut Street, R4 451A, Indianapolis, Indiana 46202

2. Division of Developmental Oncology Research, Department of Immunology, Mayo Clinic, 13-11C Guggenheim, 200 First Street Southwest, Rochester, Minnesota 55905

3. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, and Walther Cancer Institute, 635 Barnhill Drive, MS-4053, Indianapolis, Indiana 46202

4. Departments of Microbiology and Immunology and Medical and Molecular Genetics, Indiana University School of Medicine, 1044 West Walnut Street, R4 402C, Indianapolis, Indiana 46202

Abstract

ABSTRACT The phagocyte NADPH oxidase catalyzes the reduction of molecular oxygen to superoxide and is essential for microbial defense. Electron transport through the oxidase flavocytochrome is activated by the Rac effector p67 phox . Previous studies suggest that Vav1 regulates NADPH oxidase activity elicited by the chemoattractant formyl-Met-Leu-Phe (fMLP). We show that Vav1 associates with p67 phox and Rac2, but not Rac1, in fMLP-stimulated human neutrophils, correlating with superoxide production. The interaction of p67 phox with Vav1 is direct and activates nucleotide exchange on Rac, which enhances the interaction between p67 phox and Vav1. This provides new molecular insights into regulation of the neutrophil NADPH oxidase, suggesting that chemoattractant-stimulated superoxide production can be amplified by a positive feedback loop in which p67 phox targets Vav1-mediated Rac activation.

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

Link

https://journals.asm.org/doi/pdf/10.1128/MCB.00985-06

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