SMALL PROTEINS AND THE NEUTROPHIL NADPH OXIDASE

The NADPH oxidase of phagocytic cells is a multimeric enzyme complex a ctivated during phagocytosis. It catalyzes the production of the super oxide anion, precursor of many toxic oxygen metabolites involved in th e defense against microorganisms. The enzyme becomes active after asse mbly on a membrane bound flavocytochrome b of cytosolic factors p47 ph ox, p67 phox and p40 phox and of low molecular mass GTP binding protei ns. This paper reviews recent results concerning the role of two small G proteins, Rac and Rap 1A in oxidase activation. Native prenylated s mall G proteins are either in the form of a complex in which the GDP b ound G protein is associated with a guanine nucleotide dissociation in hibitor, GDI, or in an active GTP bound form able to trigger the activ ity of its effector. Rac and Rho share a common GDI. As chemotaxis, un der Rho control, and oxidase activation, under Rac control, show mutua lly exclusive signalling pathways, we propose a model where the GDI wo uld switch from one pathway to the other by sequestering either Rac or Rho.