Participation of Rac GTPase activating proteins in the deactivation of the phagocytic NADPH oxidase

Patryk Moskwa, Marie Claire Dagher, Marie Hélène Paclet, Francoise Morel, E. Ligeti

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The aim of the present study was to investigate possible mechanisms that could be involved in the deactivation of the assembled, catalytically active NADPH oxidase of phagocytic cells and thereby lead to termination of O2 •- production. Our major findings are the following: (1) Addition of GDP to the active oxidase is able to reduce O2 •- production both in the fully purified and in a semirecombinant cell-free activation system. (2) p67phox inhibits GTP hydrolysis on Rac whereas p47phox has no effect on Rac GTPase activity. (3) Soluble regulatory proteins (GTPase activating protein, guanine nucleotide dissociation inhibitor, and the Rac-binding domain of the target protein p21-activated kinase) inhibit activation of the NADPH oxidase but have no effect on electron transfer via the assembled enzyme complex. (4) Membrane-associated GTPase activating proteins (GAPs) have access also to the assembled, catalytically active oxidase. Taken together, we propose that the GTP-bound active form of Rac is required for sustained enzyme activity and that membrane-localized GAPs have a role in the deactivation of NADPH oxidase.

Original languageEnglish
Pages (from-to)10710-10716
Number of pages7
JournalBiochemistry
Volume41
Issue number34
DOIs
Publication statusPublished - Aug 27 2002

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rac GTP-Binding Proteins
GTPase-Activating Proteins
NADPH Oxidase
Guanosine Triphosphate
Oxidoreductases
Guanine Nucleotide Dissociation Inhibitors
Chemical activation
p21-Activated Kinases
Membranes
Cell-Free System
GTP Phosphohydrolases
Enzyme activity
Enzymes
Phagocytes
Protein Kinases
Hydrolysis
Membrane Proteins
Electrons
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Participation of Rac GTPase activating proteins in the deactivation of the phagocytic NADPH oxidase. / Moskwa, Patryk; Dagher, Marie Claire; Paclet, Marie Hélène; Morel, Francoise; Ligeti, E.

In: Biochemistry, Vol. 41, No. 34, 27.08.2002, p. 10710-10716.

Research output: Contribution to journalArticle

Moskwa, Patryk ; Dagher, Marie Claire ; Paclet, Marie Hélène ; Morel, Francoise ; Ligeti, E. / Participation of Rac GTPase activating proteins in the deactivation of the phagocytic NADPH oxidase. In: Biochemistry. 2002 ; Vol. 41, No. 34. pp. 10710-10716.
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