Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase.
We purified human plasma lysophospholipase D that produces physiologically active lysophosphatidic acid and showed that it is a soluble form of autotaxin, an ecto-nucleotide pyrophosphatase/phosphodiesterase, originally found as a tumor cell motility-stimulating factor. Its lower K(m) value for a lysophosphatidylcholine than that for a synthetic substrate of nucleotide suggests that lysophosphatidylcholine is a more likely physiological substrate for autotaxin and that its predicted physiological and pathophysiological functions could be mediated by its activity to produce lysophosphate acid, an intercellular mediator. Recombinant autotaxin was found to have lysophospholipase D activity; its substrate specificity and metal ion requirement were the same as those of the purified plasma enzyme. The activity of lysophospholipase D for exogenous lysophosphatidylcholine in human serum was found to increase in normal pregnant women at the third trimester of pregnancy and to a higher extent in patients in threatened preterm delivery, suggesting its roles in induction of parturition.
Tokumura
Akira
A
Faculty of Pharmaceutical Sciences, The University of Tokushima, Tokushima 770-8505, Japan. tokumura@ph.tokushima-u.ac.jp
Majima
Eiji
E
Kariya
Yuko
Y
Tominaga
Kyoko
K
Kogure
Kentaro
K
Yasuda
Katsuhiko
K
Fukuzawa
Kenji
K
D000595:Amino Acid Sequence; D000818:Animals; D002852:Chromatography, Ion Exchange; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005956:Glucose-6-Phosphate Isomerase / Q000737:chemistry / Q000378:metabolism*; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008246:Lysophospholipids / Q000378:metabolism*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes; D009711:Nucleotides / Q000378:metabolism; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry* / Q000302:isolation & purification; D011247:Pregnancy; D011755:Pyrophosphatases; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity; D013997:Time Factors; D000099189:Lysophospholipase D
D005956:Glucose-6-Phosphate Isomerase; D006023:Glycoproteins; D008246:Lysophospholipids; D009097:Multienzyme Complexes; D009711:Nucleotides; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D011994:Recombinant Proteins; D000099189:Lysophospholipase D