Isolation of a cDNA encoding human lysophosphatidic acid phosphatase that is involved in the regulation of mitochondrial lipid biosynthesis
Isolation of a cDNA encoding human lysophosphatidic acid phosphatase that is involved in the regulation of mitochondrial lipid biosynthesis
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DOI：
10.1074/jbc.274.41.29172
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发表时间：
1999-10-08
影响因子：
4.8
通讯作者：
Takenawa, T
中科院分区：
文献类型：
--
作者：
Hiroyama, R;Takenawa, T
在这项研究中，我们分离的cDNA编码溶血磷脂酸（LPA）磷酸酶（LPAP）。从编码I;PAP的cDNA推导的氨基酸序列有421个残基，包括一个假定的信号肽，是同源的酸性磷酸酶，特别是在活性位点。人LPAP与人前列腺酸性磷酸酶的氨基酸同源性为28.5%。北方印迹分析显示LPAP在肾脏、心脏、小肠、肌肉和肝脏中普遍表达。用荧光原位杂交技术获得的人类染色体图谱显示，LPAP基因定位于染色体1 q21。其中组氨酸被丙氨酸取代的突变体的活性位点和推定的信号肽缺失的LPAP没有I;PA磷酸酶活性。此外，推定的信号肽缺失的LPAP没有表现出线粒体定位。在MDCK细胞和分化的C2 C12细胞中，内源性LPAP的胞内定位部位也是线粒体。LPAP同源磷酸酶，人前列腺酸性磷酸酶，也具有LPA磷酸酶活性。LPAP稳定转染的NIH 3 T3细胞显示出较少的磷脂酸、磷脂酰甘油和心磷脂。这些结果表明，LPAP调节脂质代谢的线粒体通过水解LPA的单酰基甘油。
In this study, we isolated cDNA encoding lysophosphatidic acid (LPA) phosphatase (LPAP). The amino acid sequence deduced from the cDNA encoding I;PAP had 421 residues including a putative signal peptide and was homologous to acid phosphatase, especially at the active site. Human LPAP had 28.5% amino acid identity to human prostatic acid phosphatase. Northern blot analysis showed a ubiquitous expression of LPAP, which was marked in kidney, heart, small intestine, muscle, and liver. Human chromosome map obtained by fluorescence in situ hybridazation showed that, the gene for LPAP was localized to chromosome 1 q21. The mutant in which histidine was replaced with alanine at the active site and the putative signal peptide-deleted LPAP had no I;PA phosphatase activity. In addition, the putative signal peptide-deleted LPAP showed no mitochondrial localization. The site of intracellular localization of endogenous LPAP was also mitochondria in MDCK cells and differentiated C2C12 cells. The LPAP homologous phosphatase, human prostatic acid phosphatase, also has LPA phosphatase activity. LPAP-stable transfected NIH 3T3 cells showed less phosphatidic acid, phosphatidylglycerol, and cardiolipin. These results suggested that LPAP regulates lipid metabolism in mitochondria via the hydrolysis of LPA to monoacylglycerol.