The phosphatidylinositol-transfer protein Nir2 binds phosphatidic acid and positively regulates phosphoinositide signalling

被引:103
作者
Kim, Sohui [1 ]
Kedan, Amir [1 ]
Marom, Merav [1 ]
Gavert, Nancy [1 ]
Keinan, Omer [1 ]
Selitrennik, Michael [1 ]
Laufman, Orly [1 ]
Lev, Sima [1 ]
机构
[1] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel
基金
以色列科学基金会;
关键词
EGFR signalling; HAD; lipid second messengers; PA; phosphoinositide signalling; PHOSPHOLIPASE-D; RETINAL DEGENERATION; PLASMA-MEMBRANE; ACTIVATION; PHOSPHORYLATION; GENERATION; ENZYME;
D O I
10.1038/embor.2013.113
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Phosphatidic acid (PA) and phosphoinositides are metabolically interconverted lipid second messengers that have central roles in many growth factor (GF)-stimulated signalling pathways. Yet, little is known about the mechanisms that coordinate their production and downstream signalling. Here we show that the phosphatidylinositol (PI)-transfer protein Nir2 translocates from the Golgi complex to the plasma membrane in response to GF stimulation. This translocation is triggered by PA formation and is mediated by its C-terminal region that binds PA in vitro. We further show that depletion of Nir2 substantially reduces the PI(4,5)P2 levels at the plasma membrane and concomitantly GF-stimulated PI(3,4,5)P3 production. Finally, we show that Nir2 positively regulates the MAPK and PI3K/AKT pathways. We propose that Nir2 through its PA-binding capability and PI-transfer activity can couple PA to phosphoinositide signalling, and possibly coordinates their local lipid metabolism and downstream signalling.
引用
收藏
页码:891 / 899
页数:9
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