The ins and outs of lysophosphatidic acid signaling.
Lysophosphatidic acid (LPA) is a lipid mediator with a wide variety of biological actions, particularly as an inducer of cell proliferation, migration and survival. LPA binds to specific G-protein-coupled receptors and thereby activates multiple signal transduction pathways, including those initiated by the small GTPases Ras, Rho, and Rac. LPA signaling has been implicated in such diverse processes as wound healing, brain development, vascular remodeling and tumor progression. Knowledge of precisely how and where LPA is produced has long proved elusive. Excitingly, it has recently been discovered that LPA is generated from precursors by 'autotaxin', a once enigmatic exo-phosphodiesterase implicated in tumor cell motility. Exogenous phospholipases D can also produce LPA, which may contribute to their toxicity. Here we review recent progress in our understanding of LPA bioactivity, signaling and synthesis.
Division of Cellular Biochemistry and Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan, Amsterdam, The Netherlands. w.moolenaar@nki.nl
Wouter H
WH
Moolenaar
Laurens A
LA
van Meeteren
Ben N G
BN
Giepmans
D000818:Animals; D005956:Glucose-6-Phosphate Isomerase / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008246:Lysophospholipids / Q000737:chemistry / Q000378:metabolism*; D008564:Membrane Potentials; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000378:metabolism; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid; D015398:Signal Transduction / Q000502:physiology*; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D000099189:Lysophospholipase D
D005956:Glucose-6-Phosphate Isomerase; D006023:Glycoproteins; D008246:Lysophospholipids; D020928:Mitogen-Activated Protein Kinases; D009097:Multienzyme Complexes; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D020744:rac GTP-Binding Proteins; D018631:ras Proteins; D020741:rho GTP-Binding Proteins; D000099189:Lysophospholipase D; C032881:lysophosphatidic acid