Moolenaar W H
Division of Cellular Biochemistry, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Ann N Y Acad Sci. 2000 Apr;905:1-10. doi: 10.1111/j.1749-6632.2000.tb06532.x.
Lysophosphatidic acid (LPA) serves as the prototypic lysophospholipid mediator that acts through G-protein-coupled receptors to evoke a host of responses in numerous target cells. The hormone- and growth-factor-like activities of LPA, mediated by distinct G proteins, were discovered about 10 years ago. Since then, considerable progress has been made in our understanding of LPA receptor signaling, culminating in the recent identification of a growing family of heptahelical receptors specific for LPA and the structurally related lysolipid, sphingosine-1-phosphate (S1P). In addition to stimulating Gi-Ras-mediated cell proliferation, LPA and S1P induce rapid G alpha 12/13-RhoA-mediated cytoskeletal changes underlying such diverse responses as neurite retraction, cell rounding, and enhanced tumor cell invasiveness. LPA also triggers inhibition of gap-junctional communication. This overview focuses on how our understanding of LPA as an intercellular lipid mediator has developed during the last decade.
溶血磷脂酸（LPA）是典型的溶血磷脂介质，它通过G蛋白偶联受体发挥作用，在众多靶细胞中引发一系列反应。大约10年前发现了由不同G蛋白介导的LPA的激素样和生长因子样活性。从那时起，我们对LPA受体信号传导的理解取得了相当大的进展，最终在最近鉴定出了一个不断增加的七螺旋受体家族，这些受体对LPA和结构相关的溶血脂质鞘氨醇-1-磷酸（S1P）具有特异性。除了刺激Gi-Ras介导的细胞增殖外，LPA和S1P还诱导快速的Gα12/13-RhoA介导的细胞骨架变化，这些变化是诸如神经突回缩、细胞变圆和增强肿瘤细胞侵袭性等多种反应的基础。LPA还会引发间隙连接通讯的抑制。本综述重点关注过去十年中我们对LPA作为细胞间脂质介质的理解是如何发展的。
