The PX domains of p47phox and p40phox bind to lipid products of Pl(3)K
The PX domains of p47phox and p40phox bind to lipid products of Pl(3)K
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DOI：
10.1038/35083070
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发表时间：
2001-07-01
影响因子：
21.3
通讯作者：
Yaffe, MB
中科院分区：
文献类型：
--
作者：
Kanai, F;Liu, H;Yaffe, MB
PX结构域存在于多种与细胞膜相关的蛋白质中，但其分子功能仍不清楚。我们发现吞噬细胞NADPH氧化酶的p47 phox和p40 phox亚基中的PX结构域分别与磷脂酰肌醇-3，4-二磷酸（Ptdlns（3，4）P-2）和磷脂酰肌醇-3-磷酸（Ptdlns（3）P）结合。我们还表明，在慢性肉芽肿病患者中发现的p47 phox的PX结构域中的Arg-至-Gln突变消除了磷酸肌醇结合，就像p40 phox的PX结构域中的类似突变一样。p40 phox的PX结构域特异性地定位于Ptdlns（B）P富集的早期内体，并且这种定位被磷酸肌醇-3-OH激酶（PI（3）K）的抑制或被Arg-至-Gln点突变破坏。这些发现为理解PI（3）K在调节中性粒细胞功能和炎症中的作用以及鉴定PX结构域作为参与真核细胞信号转导事件的特异性磷酸肌醇结合模块提供了分子基础。
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 (Ptdlns(3,4)P-2) and phosphatidylinositol-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 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 Ptdlns(B)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.