Lysophosphatidic acid (LPA) receptors of the EDG family are differentially activated by LPA species: Structure–activity relationship of cloned LPA receptors

We examined the structure–activity relationship of cloned lysophosphatidic acid (LPA) receptors (endothelial cell differentiation gene (EDG) 2, EDG4, and EDG7) by measuring [Ca 2+] i in Sf9 insect cells expressing each receptor using LPA with various acyl chains bound at either the sn-1 or the sn-2...

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Veröffentlicht in:FEBS letters 2000-07, Vol.478 (1), p.159-165
Hauptverfasser: Bandoh, Koji, Aoki, Junken, Taira, Akitsu, Tsujimoto, Masafumi, Arai, Hiroyuki, Inoue, Keizo
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container_issue 1
container_start_page 159
container_title FEBS letters
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creator Bandoh, Koji
Aoki, Junken
Taira, Akitsu
Tsujimoto, Masafumi
Arai, Hiroyuki
Inoue, Keizo
description We examined the structure–activity relationship of cloned lysophosphatidic acid (LPA) receptors (endothelial cell differentiation gene (EDG) 2, EDG4, and EDG7) by measuring [Ca 2+] i in Sf9 insect cells expressing each receptor using LPA with various acyl chains bound at either the sn-1 or the sn-2 position of the glycerol backbone. For EDG7 the highest reactivity was observed with LPA with Δ9-unsaturated fatty acid (oleic (18:1), linoleic (18:2), and linolenic (18:3)) at sn-2 followed by 2-palmitoleoyl (16:1) and 2-arachidonoyl (20:4) LPA. In contrast, EDG2 and EDG4 showed broad ligand specificities, although EDG2 and EDG4 discriminated between 14:0 (myristoyl) and 16:0 (palmitoyl), and 12:0 (lauroyl) and 14:0 LPAs, respectively. EDG7 recognizes the cis double bond at the Δ9 position of octadecanoyl residues, since 2-elaidoyl (18:1, trans) and 2-petroselinoyl (18:1, cis-Δ12) LPA were poor ligands for EDG7. In conclusion, the present study demonstrates that each LPA receptor can be activated differentially by the LPA species.
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For EDG7 the highest reactivity was observed with LPA with Δ9-unsaturated fatty acid (oleic (18:1), linoleic (18:2), and linolenic (18:3)) at sn-2 followed by 2-palmitoleoyl (16:1) and 2-arachidonoyl (20:4) LPA. In contrast, EDG2 and EDG4 showed broad ligand specificities, although EDG2 and EDG4 discriminated between 14:0 (myristoyl) and 16:0 (palmitoyl), and 12:0 (lauroyl) and 14:0 LPAs, respectively. EDG7 recognizes the cis double bond at the Δ9 position of octadecanoyl residues, since 2-elaidoyl (18:1, trans) and 2-petroselinoyl (18:1, cis-Δ12) LPA were poor ligands for EDG7. In conclusion, the present study demonstrates that each LPA receptor can be activated differentially by the LPA species.</abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>10922489</pmid><doi>10.1016/S0014-5793(00)01827-5</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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subjects Amino Acid Sequence
Animals
Calcium - metabolism
Calcium Signaling - drug effects
Cell Line
Dose-Response Relationship, Drug
EDG2
EDG4
EDG7
Endothelial cell differentiation gene family
Humans
Ligands
Lysophosphatidic acid
Lysophospholipids - chemistry
Lysophospholipids - pharmacology
Molecular Sequence Data
Receptors, Cell Surface - chemistry
Receptors, Cell Surface - genetics
Receptors, Cell Surface - metabolism
Receptors, G-Protein-Coupled
Receptors, Lysophosphatidic Acid
Recombinant Fusion Proteins - chemistry
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
Spodoptera
Structure-Activity Relationship
Substrate Specificity
Transfection
title Lysophosphatidic acid (LPA) receptors of the EDG family are differentially activated by LPA species: Structure–activity relationship of cloned LPA receptors
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