Ectonucleotide pyrophosphatase/phosphodiesterase family member 2

Definition:

Hydrolyzes lysophospholipids to produce the signaling molecule lysophosphatidic acid (LPA) in extracellular fluids. Major substrate is lysophosphatidylcholine. Can also act on sphingosylphosphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility. Can hydrolyze, in vitro, bis-pNPP, to some extent pNP-TMP, and barely ATP. Involved in several motility-related processes such as angiogenesis and neurite outgrowth. Acts as an angiogenic factor by stimulating migration of smooth muscle cells and microtubule formation. Stimulates migration of melanoma cells, probably via a pertussis toxin-sensitive G protein. May have a role in induction of parturition. Possible involvement in cell proliferation and adipose tissue development (Probable). Tumor cell motility-stimulating factor. Required for LPA production in activated platelets, cleaves the sn-1 lysophospholipids to generate sn-1 lysophosphatidic acids containing predominantly 18:2 and 20:4 fatty acids. Shows a preference for the sn-1 to the sn-2 isomer of 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF).

References:

[1]. S W Nam, et al. Autotaxin (NPP-2), a metastasis-enhancing motogen, is an angiogenic factor. Cancer Res. 2001 Sep 15;61(18):6938-44. [Content Brief]

[2]. Junken Aoki, et al. Serum lysophosphatidic acid is produced through diverse phospholipase pathways. J Biol Chem. 2002 Dec 13;277(50):48737-44. [Content Brief]

[3]. Jens Hausmann, et al. Structural basis of substrate discrimination and integrin binding by autotaxin. Nat Struct Mol Biol. 2011 Feb;18(2):198-204. [Content Brief]

[4]. Gretchen Bain, et al. Selective Inhibition of Autotaxin Is Efficacious in Mouse Models of Liver Fibrosis. J Pharmacol Exp Ther. 2017 Jan;360(1):1-13. [Content Brief]

[5]. Laurens A van Meeteren, et al. Inhibition of autotaxin by lysophosphatidic acid and sphingosine 1-phosphate. J Biol Chem. 2005 Jun 3;280(22):21155-61. [Content Brief]

[6]. Adam J Stein, et al. Structural Basis for Inhibition of Human Autotaxin by Four Potent Compounds with Distinct Modes of Binding. Mol Pharmacol. 2015 Dec;88(6):982-92. [Content Brief]

[7]. M L Stracke, et al. Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein. J Biol Chem. 1992 Feb 5;267(4):2524-9. [Content Brief]

[8]. Timothy Clair, et al. Autotaxin hydrolyzes sphingosylphosphorylcholine to produce the regulator of migration, sphingosine-1-phosphate. Cancer Res. 2003 Sep 1;63(17):5446-53. [Content Brief]

[9]. Alyssa L Bolen, et al. The phospholipase A1 activity of lysophospholipase A-I links platelet activation to LPA production during blood coagulation. J Lipid Res. 2011 May;52(5):958-70. [Content Brief]

[10]. J Boucher, et al. Potential involvement of adipocyte insulin resistance in obesity-associated up-regulation of adipocyte lysophospholipase D/autotaxin expression. Diabetologia. 2005 Mar;48(3):569-77. [Content Brief]

[11]. Akira Tokumura, et al. Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase. J Biol Chem. 2002 Oct 18;277(42):39436-42. [Content Brief]

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