Phosphatidylinositol 4-phosphate 5-kinase α is a downstream effector of the small G protein ARF6 in membrane ruffle formation
Phosphatidylinositol 4-phosphate 5-kinase α is a downstream effector of the small G protein ARF6 in membrane ruffle formation
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DOI：
10.1016/s0092-8674(00)81540-8
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发表时间：
1999-11-24
期刊：
影响因子：
64.5
通讯作者：
Kanaho, Y
中科院分区：
文献类型：
--
作者：
Honda, A;Nogami, M;Kanaho, Y
磷脂酰肌醇4,5-二磷酸[PI(4,5)P-2]是一种信号磷脂，主要由磷脂酰肌醇4-磷酸5-激酶[PI(4)P5K]合成，据报道，该激酶受RhoA和Rad的调节。我们意外地发现，PI(4)P5K α的GTP γ s依赖性激活因子是小G蛋白adp -核糖基化因子（ARF），其激活严格需要磷脂酸，即磷脂酶D （PLD）的产物。在体内，ARF6，而不是ARF1或ARF5，在空间上与PI(4)P5K α重合。这种共定位发生在AIF(4)和EGF刺激后形成的褶膜中，并被显性阴性的ARF6阻断。PLD2类似地易位到褶边，磷脂酶C δ 1的PH结构域也是如此，表明局部PI(4,5)P-2升高。因此，PI(4)P5K α是ARF6的下游效应物，当ARF6被激动剂刺激激活时，它会触发多种相互作用的信号分子聚集到活跃的细胞骨架和膜重排位点。
Synthesis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P-2], a signaling phospholipid, is primarily carried out by phosphatidylinositol 4-phosphate 5-kinase [PI(4)P5K], which has been reported to be regulated by RhoA and Rad. Unexpectedly, we find that the GTP gamma S-dependent activator of PI(4)P5K alpha is the small G protein ADP-ribosylation factor (ARF) and that the activation strictly requires phosphatidic acid, the product of phospholipase D (PLD). In vivo, ARF6, but not ARF1 or ARF5, spatially coincides with PI(4)P5K alpha. This colocalization occurs in ruffling membranes formed upon AIF(4) and EGF stimulation and is blocked by dominant-negative ARF6. PLD2 similarly translocates to the ruffles, as does the PH domain of phospholipase C delta 1, indicating locally elevated PI(4,5)P-2. Thus, PI(4)P5K alpha is a downstream effector of ARF6 and when ARF6 is activated by agonist stimulation, it triggers recruitment of a diverse but interactive set of signaling molecules into sites of active cytoskeletal and membrane rearrangement.