The Rac effector p67phox regulates phagocyte NADPH oxidase by stimulating Vav1 guanine nucleotide exchange activity

Wenyu Ming, Shijun Li, Daniel D. Billadeau, Lawrence Quilliam, Mary C. Dinauer

Research output: Contribution to journalArticle

44 Citations (Scopus)

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 p67phox. Previous studies suggest that Vav1 regulates NADPH oxidase activity elicited by the chemoattractant formyl-Met-Leu-Phe (IMLP). We show that Vav1 associates with p67phox 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 p67phox and Vav1. This provides new molecular insights into regulation of the neutrophil NADPII oxidase, suggesting that chemoattractant-stimulated superoxide production can be amplified by a positive feedback loop in which p67phox targets Va1-mediated Rac activation.

Original languageEnglish
Pages (from-to)312-323
Number of pages12
JournalMolecular and Cellular Biology
Volume27
Issue number1
DOIs
StatePublished - Jan 1 2007

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Guanine Nucleotides
NADPH Oxidase
Phagocytes
Superoxides
Chemotactic Factors
Oxidoreductases
Neutrophils
methionyl-leucyl-phenylalanine
Electron Transport
Nucleotides
neutrophil cytosol factor 67K
Oxygen

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

The Rac effector p67phox regulates phagocyte NADPH oxidase by stimulating Vav1 guanine nucleotide exchange activity. / Ming, Wenyu; Li, Shijun; Billadeau, Daniel D.; Quilliam, Lawrence; Dinauer, Mary C.

In: Molecular and Cellular Biology, Vol. 27, No. 1, 01.01.2007, p. 312-323.

Research output: Contribution to journalArticle

Ming, Wenyu ; Li, Shijun ; Billadeau, Daniel D. ; Quilliam, Lawrence ; Dinauer, Mary C. / The Rac effector p67phox regulates phagocyte NADPH oxidase by stimulating Vav1 guanine nucleotide exchange activity. In: Molecular and Cellular Biology. 2007 ; Vol. 27, No. 1. pp. 312-323.
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