Waggoner D W, Xu J, Singh I, Jasinska R, Zhang Q X, Brindley D N
Department of Biochemistry (Signal Transduction Laboratories), Lipid and Lipoprotein Research Group, University of Alberta, 357 Heritage Medical Research Centre, Edmonton, Alberta T6G 2S2, Canada.
Biochim Biophys Acta. 1999 Jul 30;1439(2):299-316. doi: 10.1016/s1388-1981(99)00102-x.
This article describes the regulation of cell signaling by lipid phosphate phosphatases (LPPs) that control the conversion of bioactive lipid phosphates to their dephosphorylated counterparts. A structural model of the LPPs, that were previously called Type 2 phosphatidate phosphatases, is described. LPPs are characterized by having no Mg(2+) requirement and their insensitivity to inhibition by N-ethylmaleimide. The LPPs have six putative transmembrane domains and three highly conserved domains that define a phosphatase superfamily. The conserved domains are juxtaposed to the proposed membrane spanning domains such that they probably form the active sites of the phosphatases. It is predicted that the active sites of the LPPs are exposed at the cell surface or on the luminal surface of intracellular organelles, such as Golgi or the endoplasmic reticulum, depending where various LPPs are expressed. LPPs could attenuate cell activation by dephosphorylating bioactive lipid phosphate esters such as phosphatidate, lysophosphatidate, sphingosine 1-phosphate and ceramide 1-phosphate. In so doing, the LPPs could generate alternative signals from diacylglycerol, sphingosine and ceramide. The LPPs might help to modulate cell signaling by the phospholipase D pathway. For example, phosphatidate generated within the cell by phospholipase D could be converted by an LPP to diacylglycerol. This should change the relative balance of signaling by these two lipids. Another possible function of the LPPs relates to the secretion of lysophosphatidate and sphingosine 1-phosphate by activated platelets and other cells. These exogenous lipids activate phospholipid growth factor receptors on the surface of cells. LPP activities could attenuate cell activation by lysophosphatidate and sphingosine 1-phosphate through their respective receptors.
本文描述了脂质磷酸酶（LPPs）对细胞信号传导的调节作用，该酶可控制生物活性脂质磷酸酯向其去磷酸化对应物的转化。文中还描述了LPPs的结构模型，LPPs以前被称为2型磷脂酸磷酸酶。LPPs的特点是不需要Mg(2+)，且对N-乙基马来酰亚胺的抑制不敏感。LPPs有六个假定的跨膜结构域和三个高度保守的结构域，它们定义了一个磷酸酶超家族。保守结构域与提议的跨膜结构域并列，因此它们可能形成磷酸酶的活性位点。据预测，LPPs的活性位点暴露在细胞表面或细胞内细胞器（如高尔基体或内质网）的腔表面，这取决于各种LPPs的表达位置。LPPs可以通过使生物活性脂质磷酸酯（如磷脂酸、溶血磷脂酸、鞘氨醇1-磷酸和神经酰胺1-磷酸）去磷酸化来减弱细胞激活。这样做时，LPPs可以从二酰基甘油、鞘氨醇和神经酰胺产生替代信号。LPPs可能有助于通过磷脂酶D途径调节细胞信号传导。例如，磷脂酶D在细胞内产生的磷脂酸可以被LPP转化为二酰基甘油。这应该会改变这两种脂质信号传导的相对平衡。LPPs的另一个可能功能与活化血小板和其他细胞分泌溶血磷脂酸和鞘氨醇1-磷酸有关。这些外源性脂质激活细胞表面的磷脂生长因子受体。LPP活性可以通过溶血磷脂酸和鞘氨醇1-磷酸各自的受体减弱细胞激活。
