Xie Yuhuan, Meier Kathryn E
Department of Pharmaceutical Sciences, Washington State University, Wegner Hall, P.O. Box 646534, Pullman, Washington, DC 99163, USA.
Cell Signal. 2004 Sep;16(9):975-81. doi: 10.1016/j.cellsig.2004.03.005.
Lysophosphatidic acid (LPA) is an important lipid mediator that binds to G-protein-coupled receptors of the Edg family, inducing proliferation and migration in many cell lines. Much has been learned about pathways involved in LPA signaling, but the pathways responsible for LPA production remain to be fully resolved. Several potential routes have been proposed for LPA production. One involves the sequential actions of phopholipase D (PLD) and phospholipase A(2) (PLA(2)). Another route involves the sequential actions of PLA(2) and lysophospholipase D (lysoPLD). LysoPLD is defined as an enzyme which hydrolyzes lysophospholipids to produce LPA. Two major forms of lysoPLD, microsomal and extracellular forms, have been reported. A microsomal lysoPLD plays an important role in the metabolism of platelet-activating factor (PAF) because of its preference for alkyl-phospholipids. The extracellular form of lysoPLD coexists with its substrate, lysophosphatidylcholine (LPC), in the extracellular compartment. LysoPLDs purified from the extracellular space have recently been shown to be molecularly identical to autotaxin (ATX). ATX, an enzyme previously known to possess 5'-nucleotide pyrophosphatase and phosphodiesterase (PDE) activities, was subsequently shown to have lysoPLD activity. The unexpected linkage of the extracellular lysoPLD with ATX has raised many interesting questions. The characterization and purification of lysoPLDs are reviewed here.
溶血磷脂酸（LPA）是一种重要的脂质介质，它与Edg家族的G蛋白偶联受体结合，可诱导多种细胞系的增殖和迁移。关于LPA信号传导所涉及的途径，我们已经了解了很多，但负责LPA产生的途径仍有待完全阐明。已经提出了几种产生LPA的潜在途径。一种途径涉及磷脂酶D（PLD）和磷脂酶A2（PLA2）的顺序作用。另一种途径涉及PLA2和溶血磷脂酶D（lysoPLD）的顺序作用。LysoPLD被定义为一种将溶血磷脂水解产生LPA的酶。已经报道了lysoPLD的两种主要形式，即微粒体形式和细胞外形式。微粒体lysoPLD因其对烷基磷脂的偏好而在血小板活化因子（PAF）的代谢中起重要作用。lysoPLD的细胞外形式与其底物溶血磷脂酰胆碱（LPC）共存于细胞外区室。最近发现，从细胞外空间纯化的lysoPLD在分子上与自分泌运动因子（ATX）相同。ATX是一种先前已知具有5'-核苷酸焦磷酸酶和磷酸二酯酶（PDE）活性的酶，随后被证明具有lysoPLD活性。细胞外lysoPLD与ATX的意外联系引发了许多有趣的问题。本文综述了lysoPLD的特性和纯化方法。
