Department of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Science, Tohoku University, 6-3 Aoba Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan.
J Biochem. 2012 Jan;151(1):89-97. doi: 10.1093/jb/mvr126. Epub 2011 Oct 11.
Autotaxin (ATX) is lysophospholipase D, which converts lysophospholipids such as lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), a bioactive lipid mediator with multiple biological roles. ATX is present in high concentrations in various biological fluids and is responsible for LPA production in these fluids. The plasma ATX level is altered in some patho-physiological conditions. Three splicing isoforms of ATX have been reported so far (ATXα, β and γ). In this study, we identified and characterized ATXδ, a novel alternative splice variant of ATX, which has a four-amino acid deletion in the L2 linker region of ATXβ. ATXδ was found to be the second major isoform following ATXβ and fully active. ATXβ and ATXδ showed similar divalent cation sensitivity and cell motility-stimulating activity. ATXβ and ATXδ are present in wide range of organism from fish to mammals. Among them, only ATXδ was found in Gallus gallus and Xenopus laevis, suggesting the indispensable role of the isoform. ATXδ was expressed in various human tissues with different expression patterns from that of ATXβ. These results show that ATXδ is a second major ATX isoform sharing similar biochemical characters with the major isoform, ATXβ, and is a potential biomarker.
自分泌酶（ATX）是溶血磷脂酶 D，可将溶血磷脂如溶血磷脂酰胆碱（LPC）转化为溶血磷脂酸（LPA），这是一种具有多种生物学作用的生物活性脂质介质。ATX 在各种生物体液中浓度较高，负责这些体液中 LPA 的产生。在某些病理生理条件下，血浆 ATX 水平会发生改变。到目前为止，已经报道了 ATX 的三种剪接异构体（ATXα、β 和γ）。在这项研究中，我们鉴定并表征了 ATXδ，这是 ATX 的一种新型替代剪接变体，其在 ATXβ 的 L2 连接区有四个氨基酸缺失。ATXδ 被发现是继 ATXβ 之后的第二大同工型，具有完全活性。ATXβ 和 ATXδ 表现出相似的二价阳离子敏感性和细胞迁移刺激活性。ATXβ 和 ATXδ 存在于从鱼类到哺乳动物的广泛生物体中。其中，只有 ATXδ 在鸡和非洲爪蟾中发现，表明该同工型是不可或缺的。ATXδ 在各种人体组织中表达，其表达模式与 ATXβ 不同。这些结果表明，ATXδ 是 ATX 的第二个主要同工型，与主要同工型 ATXβ 具有相似的生化特征，是一种潜在的生物标志物。
