A novel phosphatidic acid-selective phospholipase A1 that produces lysophosphatidic acid.
Lysophosphatidic acid (LPA) is a lipid mediator with diverse biological properties, although its synthetic pathways have not been completely solved. We report the cloning and characterization of a novel phosphatidic acid (PA)-selective phospholipase A(1) (PLA(1)) that produces 2-acyl-LPA. The PLA(1) was identified in the GenBank(TM) data base as a close homologue of phosphatidylserine (PS)-specific PLA(1) (PS-PLA(1)). When expressed in insect Sf9 cells, this enzyme was recovered from the Triton X-100-insoluble fraction and did not show any catalytic activity toward exogenously added phospholipid substrates. However, culture medium obtained from Sf9 cells expressing the enzyme was found to activate EDG7/LPA(3), a cellular receptor for 2-acyl-LPA. The activation of EDG7 was further enhanced when the cells were treated with phorbol ester or a bacterial phospholipase D, suggesting involvement of phospholipase D in the process. In the latter condition, an increased level of LPA, but not other lysophospholipids, was confirmed by mass spectrometry analyses. Expression of the enzyme is observed in several human tissues such as prostate, testis, ovary, pancreas, and especially platelets. These data show that the enzyme is a membrane-associated PA-selective PLA(1) and suggest that it has a role in LPA production.
Sonoda
Hirofumi
H
Graduate School of Pharmaceutical Sciences, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Aoki
Junken
J
Hiramatsu
Tatsufumi
T
Ishida
Mayuko
M
Bandoh
Koji
K
Nagai
Yuki
Y
Taguchi
Ryo
R
Inoue
Keizo
K
Arai
Hiroyuki
H
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002384:Catalysis; D002462:Cell Membrane / Q000201:enzymology; D006801:Humans; D008246:Lysophospholipids / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D010712:Phosphatidic Acids / Q000378:metabolism*; D010741:Phospholipases A / Q000737:chemistry / Q000502:physiology*; D054466:Phospholipases A1; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D011994:Recombinant Proteins / Q000737:chemistry; D018411:Spodoptera
D008246:Lysophospholipids; D010712:Phosphatidic Acids; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D011994:Recombinant Proteins; D010741:Phospholipases A; D054466:Phospholipases A1