Brief Communication abstract
Nature Cell Biology 3, 675 - 678 (2001)
Published online: 12 June 2001 | doi:10.1038/35083070
The PX domains of p47phox and p40phox bind to lipid products of PI(3)K
Fumihiko Kanai1,5, Hui Liu1,5, Seth J. Field5,2,3, Hares Akbary1,5, Tsuyoshi Matsuo2, Glenn E. Brown1,4, Lewis C. Cantley2 & Michael B. Yaffe1,4
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)P2) 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.
- Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
- Division of Signal Transduction, Beth Israel Deaconess Medical Center, and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02215, USA
- Division of Endocrinology, Massachusetts General Hospital, Boston, Massachusetts 02114 USA
- Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
- These authors contributed equally to this work.
Correspondence to: Michael B. Yaffe1,4 e-mail: myaffe@mit.edu
