Phospholipase D1 and potential targets of its hydrolysis product, phosphatidic acid
Phospholipase D1 and potential targets of its hydrolysis product, phosphatidic acid
复制标题
DOI：
10.1042/bst0310094
复制
发表时间：
2003-02-01
影响因子：
3.9
通讯作者：
Sugars, JM
中科院分区：
文献类型：
--
作者：
Ktistakis, NT;Delon, C;Sugars, JM
磷脂酶D （PLO）将磷脂酰胆碱水解成磷脂酸（PA）和胆碱。我们的工作旨在了解PLD1的特性，并确定PA的下游靶点。在一组项目中，我们专注于膜靶向机制，并提出了一种允许PLD1定位到细胞膜内的信号层次。这些信号涉及功能性pleckstrin同源（PH）结构域及其在两个相邻半胱氨酸残基上的脂肪酰化。附近的Phox同源结构域（PX）可能调节脂肪酰化PH结构域的功能。这种复杂的信号阵列可能是在基础和信号依赖条件下PLD1靶向多个内吞和分泌膜所必需的。在另一组项目中，我们使用化学合成的PA偶联到固体载体上，以识别与该磷脂相互作用的蛋白质。从这个筛选中出现了几种蛋白质作为潜在的靶标。一些（如adp -核糖基化因子，涂层β亚基）参与运输，它们的PA亲和力可以从它们在运输过程中在膜上和膜下的调节循环来理解。其他的（鞘氨醇1-磷酸激酶和ptdins4p5 -激酶）也涉及到PLO激活的途径。其他仍然是新的蛋白质（脑特异性神经软骨素），其对PA的亲和力可能有助于了解其细胞功能。
Phospholipase D (PLO) hydrolyses phosphatidylcholine into phosphatidic acid (PA) and choline. our work aims to understand the properties of PLD1, and to identify downstream targets of PA. In one set of projects, we have focused on membrane-targeting mechanisms and have proposed a hierarchy of signals that allows PLD1 to localize to intracellular membranes. These signals involve a functional pleckstrin homology (PH) domain and its fatty acylation on two adjacent cysteine residues. A nearby Phox homology (PX) domain may modulate the function of the fatty acylated PH domain. This complex array of signals is probably necessitated by the targeting of PLD1 to multiple endocytic and secretory membranes under basal and signal-dependent conditions. in another set of projects, we have used chemically synthesized PA coupled to a solid support in order to identify proteins that interact with this phospholipid. Several proteins have emerged from this screen as potential targets. Some (e.g. ADP-ribosylation factor, coatomer beta subunit) are involved in trafficking and their PA affinity can be understood in terms of their regulated cycling on and off membranes during rounds of transport. others (sphingosine 1-phosphate kinase and PtdIns4P 5-kinase) are implicated in pathways that also involve PLO activation. Others still are novel proteins (brain-specific neurochondrin) whose affinity for PA may contribute to an understanding of their cellular function.