Journal of Lipid Research, Journal Year: 2014, Volume and Issue: 55(6), P. 1010 - 1018

Published: Feb. 19, 2014

Autotaxin (ATX), or ecto-nucleotide pyrophosphatase/phosphodiesterase-2, is a secreted lysophospholipase D (lysoPLD) that hydrolyzes extracellular lysophospholipids into the lipid mediator lysophosphatidic acid (LPA), ligand for specific G protein-coupled receptors. ATX-LPA signaling essential development and has been implicated in great diversity of (patho)physiological processes, ranging from lymphocyte homing to tumor progression. Structural functional studies have revealed what makes ATX unique lysoPLD, how binds its target cells. The catalytic domain shows characteristic bimetallic active site followed by shallow binding groove can accommodate nucleotides as well glycerol moiety lysophospholipids, deep lipid-binding pocket. In addition, an open tunnel unknown function adjacent site. Here, we discuss our current understanding structure-function relationships mechanisms, isoforms use distinct mechanisms LPA production plasma membrane, notably integrins heparan sulfate proteoglycans. We also briefly drug-like inhibitors ATX. known pyrophosphatase/phosphodiesterase (ENPP)2, belongs ENPP family. family consists seven members with structurally related domains hydrolyze phosphodiester bonds various substrates, including nucleoside triphosphates, choline phosphate esters (1Bollen M. Gijsbers R. Ceulemans H. Stalmans W. Stefan C. Nucleotide pyrophosphatases/phosphodiesterases on move.Crit. Rev. Biochem. Mol. Biol. 2000; 35: 393-432Crossref PubMed Scopus (255) Google Scholar, 2Stefan Jansen S. Bollen NPP-type ectophosphodiesterases: unity diversity.Trends Sci. 2005; 30: 542-550Abstract Full Text PDF (302) 3Zimmermann Zebisch Strater N. 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