title: Autotaxin--an LPA producing enzyme with diverse functions.
abstract: Autotaxin (ATX) is an ecto-enzyme responsible for lysophosphatidic acid (LPA) production in blood. ATX is present in various biological fluids such as cerebrospinal and seminal fluids and accounts for bulk LPA production in these fluids. ATX is a member of the nucleotide pyrophosphatase/phosphodiesterase (NPP) family and was originally isolated from conditioned medium of melanoma cells as an autocrine motility stimulating factor. LPA, a second-generation lipid mediator, binds to its cognate G protein-coupled receptors through which it exerts a number of biological functions including influencing cell motility and proliferation stimulating activity. Some of the biological roles of LPA can be mediated by ATX. However, there are other LPA-producing pathways independent of ATX. The accumulating evidences for physiological and pathological functions of ATX strongly support that ATX is an important therapeutic target. This review summarizes the historical aspects, structural basis, pathophysiological functions identified in mice studies and clinical relevance discovered by measuring the blood ATX level in human. The general features and functions of each NPP family member will be also briefly reviewed. The presence of the ATX gene in other model organisms and recently developed ATX inhibitors, both of which will be definitely useful for further functional analysis of ATX, will also be mentioned.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Nakanaga
authors.forename: Kotaro
authors.initials: K
authors.lastname: Hama
authors.forename: Junken
authors.initials: J
authors.lastname: Aoki
mesh_terms: D000818:Animals; D047108:Embryonic Development / Q000187:drug effects; D006801:Humans; D008246:Lysophospholipids / Q000096:biosynthesis* / Q000737:chemistry; D023421:Models, Animal; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000494:pharmacology; D013379:Substrate Specificity / Q000187:drug effects
chemical_list: D008246:Lysophospholipids; D054852:Small Molecule Libraries; D010727:Phosphoric Diester Hydrolases; C032881:lysophosphatidic acid