부산대학교 도서관

The production of reactive oxygen species (ROS) by neutrophils has a vital role in defence against a range of infectious agents, and is driven by the assembly of a multi-protein complex containing a minimal core of five proteins: the two membrane-bound subunits of cytochrome b[sub 558] (gp91[sup phox] and p22[sup phox]) and three soluble factors (GTP-Rac, p47[sup phox] and p67[sup phox] (refs 1, 2). This minimal complex can reconstitute ROS formation in vitro in the presence of non-physiological amphiphiles such as SDS. p40[sup phox] has subsequently been discovered as a binding partner for p67[sup phox] (ref. 3), but its role in ROS formation is unclear. Phosphoinositide-3-OH kinases (PI(3)Ks) have been implicated in the intracellular signalling pathways coordinating ROS formation but through an unknown mechanism. We show that the addition of p40[sup phox] to the minimal core complex allows a lipid product of PI(3)Ks, phosphatidylinositol 3-phosphate (PtdIns(3)P), to stimulate specifically the formation of ROS. This effect was mediated by binding of PtdIns(3)P to the PX domain of p40[sup phox]. These results offer new insights into the roles for PI(3)Ks and p40[sup phox] in ROS formation and define a cellular ligand for the orphan PX domain. [ABSTRACT FROM AUTHOR]