Eberhardt C, Gray P W, Tjoelker L W
ICOS Corporation, Bothell, WA 98021, USA.
Adv Exp Med Biol. 1999;469:351-6. doi: 10.1007/978-1-4615-4793-8_51.
In this report we describe a pair of human LPAAT isozymes. These isozymes are encoded by distinct genes located on different chromosomes, but share sequence homology, substrate specificity, and intracellular location. The biological value of maintaining the two closely related LPAAT genes in the human genome is not clear. We find that both isozymes are widely expressed, although expression levels do diverge significantly in tissues such as the liver, placenta, testes, and pancreas. We also find that, at least in the artificial system of over-expression in COS7 cells, both isozymes localize to the ER membrane. Thus, distinct tissue-specific or subcellular compartment-specific roles for the two isozymes are not supported by the current experimental evidence. It does remain possible that induction of expression or subcellular translocation of one or the other isozyme may distinguish their functions. A survey of a limited number of acyl CoA substrates indicates that the two isozymes display similar substrate specificities, although slight differences are suggested by the data. However, extensive analysis of both isozymes with multiple substrates in the same assay system will be required to detect physiologically relevant differences in substrate specificity. LPA and PA are central intermediates in phospholipid biogenesis. Furthermore, they have the capacity to mediate signaling both between and within cells. The importance of these mediators is reflected in the growing body of literature dedicated to unraveling the mechanistic basis for their actions. Until recently, the field has been hampered by a dearth of reagents appropriate for the molecular dissection of the LPA and PA metabolic and signaling pathways in eukaryotes. However, the recent cloning of possible LPA receptors will promote further understanding of LPA signaling. Similarly, the recent appearance of LPAAT homologs in the EST database has prompted a flurry of reports describing their characterization. These clones will afford opportunity for defining the function of LPAAT in eukaryotic phospholipid metabolism.
在本报告中，我们描述了一对人溶血磷脂酸酰基转移酶（LPAAT）同工酶。这些同工酶由位于不同染色体上的不同基因编码，但具有序列同源性、底物特异性和细胞内定位。在人类基因组中保留两个密切相关的LPAAT基因的生物学价值尚不清楚。我们发现这两种同工酶均广泛表达，尽管在肝脏、胎盘、睾丸和胰腺等组织中的表达水平确实存在显著差异。我们还发现，至少在COS7细胞的过表达人工系统中，这两种同工酶都定位于内质网（ER）膜。因此，目前的实验证据不支持这两种同工酶具有不同的组织特异性或亚细胞区室特异性作用。一种或另一种同工酶的表达诱导或亚细胞易位仍有可能区分它们的功能。对有限数量的酰基辅酶A底物的调查表明，这两种同工酶表现出相似的底物特异性，尽管数据表明存在细微差异。然而，需要在同一检测系统中对这两种同工酶与多种底物进行广泛分析，以检测底物特异性方面的生理相关差异。溶血磷脂酸（LPA）和磷脂酸（PA）是磷脂生物合成的核心中间体。此外，它们有能力介导细胞间和细胞内的信号传导。这些介质的重要性体现在致力于揭示其作用机制基础的文献不断增加。直到最近，该领域一直受到缺乏适用于真核生物中LPA和PA代谢及信号通路分子剖析的试剂的阻碍。然而，最近可能的LPA受体的克隆将促进对LPA信号传导的进一步理解。同样，EST数据库中最近出现的LPAAT同源物促使了一系列描述其特征的报告。这些克隆将为确定LPAAT在真核生物磷脂代谢中的功能提供机会。
