Abstract：
:PX domains are found in a variety of proteins that associate with cell membranes, but their molecular function has remained obscure. We show here that the PX domains in p47phox and p40phox subunits of the phagocyte NADPH oxidase bind to phosphatidylinositol-3,4-bisphosphate (PtdIns(3,4)P(2)) and phosphatidylinositol-3-phosphate (PtdIns(3)P), respectively. We also show that an Arg-to-Gln mutation in the PX domain of p47phox, which is found in patients 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 PtdIns(3)P-enriched early endosomes, and this localization is disrupted by inhibition of phosphoinositide-3-OH kinase (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 neutrophil function and inflammation, and to identify PX domains as specific phosphoinositide-binding modules involved in signal transduction events in eukaryotic cells.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Kanai F,Liu H,Field SJ,Akbary H,Matsuo T,Brown GE,Cantley LC,Yaffe MBdoi
10.1038/35083070keywords:
subject
Has Abstractpub_date
2001-07-01 00:00:00pages
675-8issue
7eissn
1465-7392issn
1476-4679pii
35083070journal_volume
3pub_type
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