Small G proteins and the neutrophil NADPH oxidase.
The NADPH oxidase of phagocytic cells is a multimeric enzyme complex activated during phagocytosis. It catalyzes the production of the superoxide anion, precursor of many toxic oxygen metabolites involved in the defense against microorganisms. The enzyme becomes active after assembly on a membrane bound flavocytochrome b of cytosolic factors p47 phox, p67 phox and p40 phox and of low molecular mass GTP binding proteins. This paper reviews recent results concerning the role of two small G proteins, Rac and Rap 1A in oxidase activation. Native prenylated small G proteins are either in the form of a complex in which the GDP bound G protein is associated with a guanine nucleotide dissociation inhibitor, GDI, or in an active GTP bound form able to trigger the activity of its effector. Rac and Rho share a common GDI. As chemotaxis, under Rho control, and oxidase activation, under Rac control, show mutually exclusive signalling pathways, we propose a model where the GDI would switch from one pathway to the other by sequestering either Rac or Rho.
Dagher
M C
MC
CEA/Laboratoire de Biochimie, URA-CNRS 1130, Département de Biologie Moléculaire et Structurale, Centre d'Etudes Nucléaires de Grenoble, France.
Fuchs
A
A
Bourmeyster
N
N
Jouan
A
A
Vignais
P V
PV
D000818:Animals; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D008970:Molecular Weight; D009247:NADH, NADPH Oxidoreductases / Q000097:blood*; D019255:NADPH Oxidases; D009504:Neutrophils / Q000201:enzymology*; D010586:Phagocytes / Q000201:enzymology; D016897:Respiratory Burst; D013481:Superoxides / Q000097:blood
D013481:Superoxides; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D019204:GTP-Binding Proteins