Isolation of a cDNA encoding human lysophosphatidic acid phosphatase that is involved in the regulation of mitochondrial lipid biosynthesis.
In this study, we isolated cDNA encoding lysophosphatidic acid (LPA) phosphatase (LPAP). The amino acid sequence deduced from the cDNA encoding LPAP 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 LPA 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.
Hiroyama
M
M
Department of Biochemistry, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Takenawa
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001921:Brain / Q000201:enzymology; D002460:Cell Line; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D003001:Cloning, Molecular; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008055:Lipids / Q000096:biosynthesis*; D008246:Lysophospholipids / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D009154:Mutation; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000235:genetics*; D021382:Protein Sorting Signals / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D008055:Lipids; D008246:Lysophospholipids; D021382:Protein Sorting Signals; D012333:RNA, Messenger; C076020:lysophosphatidic acid phosphatase; D010744:Phosphoric Monoester Hydrolases