磷脂酰肌醇4,5 - 二磷酸将胞质IVA组磷脂酶A2锚定到核周膜上，并降低其在活细胞中转位所需的钙含量。
Phosphatidylinositol 4,5-bisphosphate anchors cytosolic group IVA phospholipase A2 to perinuclear membranes and decreases its calcium requirement for translocation in live cells.
作者信息
Casas Javier, Gijón Miguel A, Vigo Ana G, Crespo Mariano Sánchez, Balsinde Jesús, Balboa María A
机构信息
Institute of Molecular Biology and Genetics, Spanish Research Council, 47003 Valladolid, Spain.
出版信息
Mol Biol Cell. 2006 Jan;17(1):155-62. doi: 10.1091/mbc.e05-06-0545. Epub 2005 Oct 12.
The eicosanoids are centrally involved in the onset and resolution of inflammatory processes. A key enzyme in eicosanoid biosynthesis during inflammation is group IVA phospholipase A2 (also known as cytosolic phospholipase A2alpha, cPLA2alpha). This enzyme is responsible for generating free arachidonic acid from membrane phospholipids. cPLA2alpha translocates to perinuclear membranes shortly after cell activation, in a process that is governed by the increased availability of intracellular Ca2+. However, cPLA2alpha also catalyzes membrane phospholipid hydrolysis in response to agonists that do not mobilize intracellular Ca2+. How cPLA2alpha interacts with membranes under these conditions is a major, still unresolved issue. Here, we report that phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] promotes translocation of cPLA2alpha to perinuclear membranes of intact cells in a manner that is independent of rises in the intracellular Ca2+ concentration. PtdIns(4,5)P2 anchors the enzyme to perinuclear membranes and allows for a proper interaction with its phospholipid substrate to release arachidonic acid.
类二十烷酸在炎症过程的发生和消退中起核心作用。炎症期间类二十烷酸生物合成中的一种关键酶是IVA组磷脂酶A2（也称为胞质磷脂酶A2α，cPLA2α）。这种酶负责从膜磷脂中生成游离花生四烯酸。细胞激活后不久，cPLA2α会转位至核周膜，这一过程受细胞内Ca2+可用性增加的调控。然而，cPLA2α也会响应不调动细胞内Ca2+的激动剂催化膜磷脂水解。在这些条件下cPLA2α如何与膜相互作用是一个主要的、仍未解决的问题。在此，我们报告磷脂酰肌醇4,5-二磷酸[PtdIns(4,5)P2]以独立于细胞内Ca2+浓度升高的方式促进cPLA2α转位至完整细胞的核周膜。PtdIns(4,5)P2将该酶锚定在核周膜上，并使其能够与其磷脂底物进行适当相互作用以释放花生四烯酸。
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