The PX domains of p47phox and p40phox bind to lipid products of Pl(3)K

Citation
F. Kanai et al., The PX domains of p47phox and p40phox bind to lipid products of Pl(3)K, NAT CELL BI, 3(7), 2001, pp. 675-678
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
NATURE CELL BIOLOGY
ISSN journal
1465-7392 → ACNP
Volume
3
Issue
7
Year of publication
2001
Pages
675 - 678
Database
ISI
SICI code
1465-7392(200107)3:7<675:TPDOPA>2.0.ZU;2-2
Abstract
PX domains are found in a variety of proteins that associate with cell memb ranes, but their molecular function has remained obscure. We show here that the PX domains in p47phox and p40phox subunits of the phagocyte NADPH oxid ase bind to phosphatidylinositol-3,4-bisphosphate (Ptdlns(3,4)P-2) and phos phatidylinositol-3-phosphate (Ptdlns(3)P), respectively. We also show that an Arg-to-Gln mutation in the PX domain of p47phox, which is found in patie nts with chronic granulomatous disease, eliminates phosphoinositide binding , as does the analogous mutation in the PX domain of p40phox, The PX domain of p40phox localizes specifically to Ptdlns(B)P-enriched early endosomes, and this localization is disrupted by inhibition of phosphoinositide-3-OH k inase (PI(3)K) or by the Arg-to-Gln point mutation. These findings provide a molecular foundation to understand the role of PI(3)K in regulating neutr ophil function and inflammation, and to identify PX domains as specific pho sphoinositide-binding modules involved in signal transduction events in euk aryotic cells.