Biological roles of lysophosphatidic acid signaling through its production by autotaxin.
Lysophosphatidic acid (LPA) exhibits a wide variety of biological functions as a bio-active lysophospholipid through G-protein-coupled receptors specific to LPA. Currently at least six LPA receptors are identified, named LPA(1) to LPA(6), while the existence of other LPA receptors has been suggested. From studies on knockout mice and hereditary diseases of these LPA receptors, it is now clear that LPA is involved in various biological processes including brain development and embryo implantation, as well as patho-physiological conditions including neuropathic pain and pulmonary and renal fibrosis. Unlike sphingosine 1-phosphate, a structurally similar bio-active lysophospholipid to LPA and produced intracellularly, LPA is produced by multiple extracellular degradative routes. A plasma enzyme called autotaxin (ATX) is responsible for the most of LPA production in our bodies. ATX converts lysophospholipids such as lysophosphatidylcholine to LPA by its lysophospholipase D activity. Recent studies on ATX have revealed new aspects of LPA. In this review, we highlight recent advances in our understanding of LPA functions and several aspects of ATX, including its activity, expression, structure, biochemical properties, the mechanism by which it stimulates cell motility and its pahto-physiological function through LPA production.
Okudaira
Shinichi
S
Department of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Science, Tohoku University, 6-3 Aoba Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan.
Yukiura
Hiroshi
H
Aoki
Junken
J
D000818:Animals; D002465:Cell Movement; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry / Q000378:metabolism*; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism; D015398:Signal Transduction; D000099189:Lysophospholipase D
D008246:Lysophospholipids; D010727:Phosphoric Diester Hydrolases; D049368:Receptors, Lysophosphatidic Acid; D000099189:Lysophospholipase D; C032881:lysophosphatidic acid