title: Cloning and characterization of DPPL1 and DPPL2, representatives of a novel type of mammalian phosphatidate phosphatase.
abstract: Phosphatidate phosphatase (PAP) enzymes are classified as either Mg(2+)-dependent (PAP1) or Mg(2+)-independent (PAP2) with respect to their Mg(2+) cofactor requirement for catalytic activity. Sensitivity to the thioreactive compound N-ethylmaleimide (NEM) has also been used to differentiate PAP1 (NEM-sensitive) from PAP2 (NEM-insensitive) activity in mammalian cells. We report here the cloning and initial characterization of DPPL1 and DPPL2, representatives of a novel type of mammalian phosphatidate phosphatase. Both DPPL1 and DPPL2 show greater homology to a yeast diacylglycerol pyrophosphate (DGPP) phosphatase, DPP1, than to known phosphatidate phosphatases of mammals. Like the yeast DPP1 protein, both DPPL1 and DPPL2 proteins show broad substrate specificity, but DGPP is the preferred substrate compared with LPA and PA. These reactions are Mg(2+)-independent, but unlike DPP1 and mammalian PAP2, they are sensitive to NEM. DPPL1 mRNA is ubiquitously expressed in various tissues and cells, but DPPL2 mRNA is restricted to several tissues including the brain, kidney and testis, and it is preferentially expressed in endothelial cells. Immunohistological staining of synovium containing vessels, plasma cells and lymphocytes revealed specific expression of DPPL2 protein in the endothelium. Collectively, our work indicates that DPPL1 and DPPL2 represent a novel type of mammalian phosphatidate phosphatase.
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada-cho, Shinjuku, Tokyo, 162-0054, Japan. masahiro.takeuchi@jp.astellas.com
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Harigai
authors.forename: Shigeki
authors.initials: S
authors.lastname: Momohara
authors.forename: Evelyn
authors.initials: E
authors.lastname: Ball
authors.forename: Jumpei
authors.initials: J
authors.lastname: Abe
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Furuichi
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D042783:Endothelial Cells / Q000378:metabolism; D005033:Ethylmaleimide / Q000494:pharmacology; D006801:Humans; D008274:Magnesium / Q000378:metabolism*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009928:Organ Specificity; D000073718:Pancreatitis-Associated Proteins; D010711:Phosphatidate Phosphatase / Q000235:genetics / Q000378:metabolism*; D011755:Pyrophosphatases / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D013583:Synovial Membrane / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D012333:RNA, Messenger; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C519642:DPP1 protein, S cerevisiae; C523992:PLPP4 protein, human; C523991:PLPP5 protein, human; D010711:Phosphatidate Phosphatase; D011755:Pyrophosphatases; D008274:Magnesium; D005033:Ethylmaleimide