TY - JOUR
T1 - Autotaxin-An LPA producing enzyme with diverse functions
AU - Nakanaga, Keita
AU - Hama, Kotaro
AU - Aoki, Junken
N1 - Funding Information:
National Institute of Biomedical Innovation (to J. A.); PRESTO (Japan Science and Technology Corporation) (to J. A.); Grant-in-Aid for Scientific Research (the Ministry of Education, Science, Sports and Culture of Japan) (to K. H. and J. A.).
PY - 2010/7
Y1 - 2010/7
N2 - 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.
AB - 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.
KW - G protein-coupled receptor
KW - autotaxin
KW - lysophosphatidic acid
KW - nucleotide pyrophosphatase
KW - phosphodiesterase
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U2 - 10.1093/jb/mvq052
DO - 10.1093/jb/mvq052
M3 - Review article
C2 - 20495010
AN - SCOPUS:77954391618
VL - 148
SP - 13
EP - 24
JO - Journal of Biochemistry
JF - Journal of Biochemistry
SN - 0021-924X
IS - 1
ER -