Ptdlns(3)P regulates the neutrophil oxidase complex by binding to the PX domain of p40phox Journal Article
| Authors: | Ellson, C. D.; Gobert-Gosse, S.; Anderson, K. E.; Davidson, K.; Erdjument-Bromage, H.; Tempst, P.; Thuring, J. W.; Cooper, M. A.; Lim, Z. Y.; Holmes, A. B.; Gaffney, P. R. J.; Coadwell, J.; Chilvers, E. R.; Hawkins, P. T.; Stephens, L. R. |
| Article Title: | Ptdlns(3)P regulates the neutrophil oxidase complex by binding to the PX domain of p40phox |
| Abstract: | 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 b558 (gp91phox and p22phox) and three soluble factors (GTP-Rac, p47phox and p67phox (refs 1, 2). This minimal complex can reconstitute ROS formation in vitro in the presence of non-physiological amphiphiles such as SDS. p40phox has subsequently been discovered as a binding partner for p67phox (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 formation4,5 but through an unknown mechanism. We show that the addition of p40phox to the minimal core complex allows a lipid product of PI(3)Ks, phosphatidylinositol 3-phosphate (Ptdlns(3)P), to stimulate specifically the formation of ROS. This effect was mediated by binding of Ptdlns(3)P to the PX domain6 of p40phox. These results offer new insights into the roles for PI(3)Ks and p40phox in ROS formation and define a cellular ligand for the orphan PX domain. |
| Keywords: | signal transduction; controlled study; unclassified drug; nonhuman; protein domain; animal cell; animal; metabolism; animals; infection; protein assembly; lipid; protein binding; in vitro study; drug effect; enzymology; phosphatidylinositol 3 kinase; animalia; blood; chemistry; enzyme regulation; neutrophil; membrane protein; ligand; reactive oxygen metabolite; phosphoproteins; binding site; neutrophils; protein structure, tertiary; binding sites; immunity; protein subunit; oxidoreductase; superoxide; superoxides; oxidoreductases; protein tertiary structure; phosphoprotein; swine; oxidation reduction reaction; oxidation-reduction; rac protein; membranes, artificial; protein p40; amphophile; phosphatidylinositol 3 phosphate; artificial membrane; dodecyl sulfate sodium; priority journal; article; protein p47; sus scrofa; phosphatidylinositol phosphates; protein p67; cytochrome b558; cytochrome b; neutrophil cytosol factor 40k; polyphosphoinositide; cytochrome b group |
| Journal Title: | Nature Cell Biology |
| Volume: | 3 |
| Issue: | 7 |
| ISSN: | 1465-7392 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2001-07-01 |
| Start Page: | 679 |
| End Page: | 682 |
| Language: | English |
| DOI: | 10.1038/35083076 |
| PUBMED: | 11433301 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
