Lipid phosphate phosphatases and lipid phosphate signalling
Lipid phosphate phosphatases and lipid phosphate signalling
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DOI：
10.1042/bst0331370
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发表时间：
2005-12-01
影响因子：
3.9
通讯作者：
Pyne, NJ
中科院分区：
文献类型：
--
作者：
Pyne, S;Long, JS;Pyne, NJ
哺乳动物 LPPS（脂质磷酸酶）是属于脂质磷酸酶/磷酸转移酶超家族的整合膜蛋白。它们在体外具有广泛的底物特异性，可对 PA（磷脂酸）、S1P（鞘氨醇 1-磷酸）、LPA（溶血磷脂酸）等进行去磷酸化。其生理作用可能包括通过胞外活性（即细胞外 S1P 和 LPA 去磷酸化）减弱 S1P 和 LPA 刺激的信号传导，从而限制 LPA 和 S1P 特异性的激活细胞表面的 G 蛋白偶联受体。然而，我们最近的工作表明，LPP2 和 LPP3 的细胞内作用可能是 HEK-293（人胚胎肾 293）细胞激动剂刺激的 p42/p44 丝裂原激活蛋白激酶活化减少的原因。这可能涉及 PA 和 S1P 基础水平分别降低以及应激条件（血清剥夺）下早期凋亡表型的存在。此外，我们描述了一个模型，其中 LPP2（而非 LPP3）可能与磷脂酶 D1 衍生的 PA 依赖性鞘氨醇激酶 1 向核周区室的募集功能相关。我们还考虑了 LPP 的潜在监管机制，其中可能涉及寡聚化。最后，我们强调 LPP 生物学的许多方面仍有待完全定义。
Mammalian LPPS (lipid-phosphate phosphatases) are integral membrane proteins that belong to a superfamily of lipid phosphatases/phosphotransferases. They have broad substrate specificity in vitro, dephosphorylating PA (phosphatidic acid), S1P (sphingosine 1-phosphate), LPA (lysophosphatidic acid) etc. Their physiological role may include the attenuation of S1P- and LPA-stimulated signalling by virtue of an ecto-activity (i.e. dephosphorylation of extracellular S1P and LPA), thereby limiting the activation of LPA and S1P-specific G-protein-coupled receptors at the cell surface. However, our recent work suggests that an intracellular action of LPP2 and LPP3 may account for the reduced agonist-stimulated p42/p44 mitogen-activated protein kinase activation of HEK-293 (human embryonic kidney 293) cells. This may involve a reduction in the basal levels of PA and S1P respectively and the presence of an early apoptotic phenotype under conditions of stress (serum deprivation). Additionally, we describe a model whereby LPP2, but not LPP3, may be functionally linked to the phospholipase D1-derived PA-dependent recruitment of sphingosine kinase 1 to the perinuclear compartment. We also consider the potential regulatory mechanisms for LPPs, which may involve oligomerization. Lastly, we highlight many aspects of the LPP biology that remain to be fully defined.