Characterization of a human lysophosphatidic acid acyltransferase that is encoded by a gene located in the class III region of the human major histocompatibility complex
Characterization of a human lysophosphatidic acid acyltransferase that is encoded by a gene located in the class III region of the human major histocompatibility complex
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DOI：
10.1074/jbc.273.7.4096
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发表时间：
1998-02-13
影响因子：
4.8
通讯作者：
Campbell, RD
中科院分区：
文献类型：
--
作者：
Aguado, B;Campbell, RD
对应于位于人主要组织相容性复合体（MHC）的III类区域（染色体带6p21.3）中的许多基因的cDNA克隆的序列分析表明，G15基因编码283个氨基酸的多肽，其在整个多肽上与来自不同酵母、植物和细菌物种的溶血磷脂酸酰基转移酶（LPAAT）具有显著的同源性，MHC编码的人LPAAT（hLPAAT α）的氨基酸序列与最近描述的hLPAAT（Eberhardt，C.，格雷，P.W.，和Tjoelker，L. W.（1991）J，Biol.Chem.272，20299 - 20305），其由位于染色体9p34.3上的基因编码，LPAAT是在脂质代谢中将溶血磷脂酸（LPA）转化为磷脂酸（PA）的酶，hEPAAT α多肽在杆状病毒系统和哺乳动物细胞中的表达表明，它是一种细胞内蛋白，含有LPAAT活性。使用不同的酰基受体和酰基供体作为底物，在不同的LPAAT酶促测定中分析来自过表达hLPAAT α的昆虫细胞的细胞提取物。发现这些细胞提取物含有与对照细胞提取物相比多至5倍的LPAAT活性，表明hLPAAT α特异性地将LPA转化为PA，掺入具有不同亲和力的不同酰基-CoA，用共聚焦免疫荧光法发现在哺乳动物中国仓鼠卵巢细胞Pine中表达的hLPAAT α多肽定位于内质网。由于已知EPA抗PA在细胞内信号传导和炎症中的作用，hLPAAT α基因代表了一些MHC相关疾病的候选基因。
Sequence analysis of cDNA clones corresponding to a number of genes located in the class III region of the human major histocompatibility complex (MHC), in the chromosome band 6p21.3, has shown that the G15 gene encodes a 283-amino acid polypeptide with significant homology over the entire polypeptide with the enzyme lysophosphatidic acid acyltransferase (LPAAT) from different yeast, plant, and bacterial species, The amino acid sequence of the MHC-encoded human LPAAT (hLPAAT alpha) is 48% identical to the recently described hLPAAT (Eberhardt, C., Gray, P. W., and Tjoelker, L. W. (1991) J, Biol. Chem. 272, 20299 - 20305), which is encoded by a gene located on chromosome 9p34.3, LPAAT is the enzyme that in lipid metabolism converts lysophosphatidic acid (LPA) into phosphatidic acid (PA), The expression of the hEPAAT alpha polypeptide in the baculovirus system and in mammalian cells has shown that it is an intracellular protein that contains LPAAT activity. Cell extracts from insect cells overexpressing hLPAAT alpha were analyzed in different LPAAT enzymatic assays using as substrates, different acyl acceptors and acyl donors, These cell extracts were found to contain up to 5-fold more LPAAT activity compared with control cell extracts, indicating that the hLPAAT alpha specifically converts LPA into PA, incorporating different acyl-CoAs with different affinities, The hLPAAT alpha polypeptide expressed in the mammalian Chinese hamster ovary cell Pine was found, by confocal immunofluorescence, to be localized in the endoplasmic reticulum, Due to the known role of EPA anti PA in intracellular signaling and inflammation, the hLPAAT alpha gene represents a candidate gene for some MHC-associated diseases.