Regulation of mammalian physiology, development, and disease by the sphingosine 1-phosphate and lysophosphatidic acid receptors

VA Blaho, T Hla - Chemical reviews, 2011 - ACS Publications
Chemical reviews, 2011ACS Publications
The moniker lysophospholipid incorporates two broad families of membrane-derived lipids:
the glycerophospholipids and the sphingolipids. 1 Primary representatives of these two arms
are lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), the majority of whose
activities are mediated via multiple G-protein-coupled receptors with a high degree of
specificity for either LPA or S1P. 2, 3 Unlike S1P, which is a single molecular species (2S-
amino-1-(dihydrogen phosphate)-4E-octadecene-1, 3R-diol), LPA (1-O-acyl-2-hydroxy-sn …
The moniker lysophospholipid incorporates two broad families of membrane-derived lipids: the glycerophospholipids and the sphingolipids. 1 Primary representatives of these two arms are lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), the majority of whose activities are mediated via multiple G-protein-coupled receptors with a high degree of specificity for either LPA or S1P. 2, 3 Unlike S1P, which is a single molecular species (2S-amino-1-(dihydrogen phosphate)-4E-octadecene-1, 3R-diol), LPA (1-O-acyl-2-hydroxy-sn-glycero-3-phosphate) is actually a diverse group of molecules consisting of either a saturated (eg, 16: 0, 18: 0) or unsaturated (eg, 16: 1, 18: 1, 18: 2, 20: 4) fatty acid chain esterified at the sn-1 or sn-2 position of a glycerol backbone. 4, 5 This can also be modified to alkyl or alkenyl at the sn-1 position. 6 Other bioactive members of the LP family include the LPA analogues cyclic phosphatidic acid (cPA), sphigosylphosphotidylcholine (SPC), lysophosphatidylcholine (LPC), lysophosphatidylserine (LPS), and lysophosphatidylinositol (LPI). 1, 5, 7 Numerous emerging reports indicate roles in mammalian biology for other, less well-characterized LP members, as well. 8 In the past decade, our understanding of LP biology has expanded exponentially, fueled by the identification of LP receptors, generation and analysis of LPA-and S1P-receptor knockout mice, and small molecule compounds functioning as receptor-specific agonists or antagonists. 3, 9, 10
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