Structural organization of mammalian lipid phosphate phosphatases: implications for signal transduction

被引:108
作者
Waggoner, DW
Xu, J
Singh, I
Jasinska, R
Zhang, QX
Brindley, DN
机构
[1] Univ Alberta, Dept Biochem, Signal Transduct Labs, Lipid & Lipoprot Res Grp, Edmonton, AB T6G 2S2, Canada
[2] Cell Therapeut Inc, Seattle, WA 98119 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS | 1999年 / 1439卷 / 02期
基金
英国医学研究理事会;
关键词
ceramide; 1-phosphate; Edg receptor; lysophosphatidate; phosphatidate; sphingosine;
D O I
10.1016/S1388-1981(99)00102-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 Mg2+ 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. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:299 / 316
页数:18
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