The Edg family of G-Protein Coupled ReceptorsThe endothelial cell differentiation gene (Edg) family of G-protein coupled receptors (GPCR) function as receptors for Lysophosphatidic acid (LPA) and structurally related sphingosine-1-phosphate (S1P). LPA and S1P are predominantly released by activated platelets and are present in blood plasma and serum, mainly bound to albumin and lipoprotein. Both LPA and S1P mediate similar biological cell responses including cell proliferation, migration, differentiation and apoptosis. LPA is a multifunctional signalling molecule that is involved in multiple biological processes including inflammation, platelet activation, wound healing and tissue regeneration (1). S1P also elicits a wide variety of responses by cells and regulates a wide range of biological process including cell proliferation, angiogenesis, cardiac development, immunity and cell motility (2). Dysregulation of S1P signalling is thought to contribute to the pathology of a wide range of diseases including cancer, diabetes, atherosclerosis, osteoporosis and progression of autoimmune conditions such as multiple sclerosis (3).
The diverse actions of LPA and S1P are mediated primarily through the binding of Edg receptors, and the regulation of various signalling pathways. Edg receptors are developmentally regulated and differentially expressed in cells, tissues and organs. Two subfamilies of Edg receptors exist based on their structure and function. The S1P receptor subfamily comprises Edg1, Edg3, Edg5, Edg6 and Edg8, which have been re-named spingosine-1-phosphate receptors S1P1, S1P3, S1P2, S1P4 and S1P5 respectively. Whereas the LPA receptor subfamily comprise Edg2, Edg4 and Edg7, which have been re-named lysophosphatidic acid receptors LPA1, LPA2 and LPA3 respectively.
Three Edg/LPA receptors have been identified for LPA. LPA1 (Edg2), is widely expressed. It is found in most tissues with the highest expression in brain and heart. On binding with LPA, LPA1 (Edg2) couples to heterotrimeric G proteins Gi/o, Gq/11 and G12/13. Loss of LPA1 receptor function has been linked to a range of pathological conditions including cancer, neuropathic pain and male infertility (4). LPA2 (Edg4) is predominantly found in the testes, prostate, pancreas, spleen and thymus. Whereas LPA3 (Edg7) is found in testes, prostate, pancreas, heart and lung. LPA2 (Edg4) and LPA3 (Edg7) couple G-proteins Gi/o and Gq to activate similar signalling pathways to LPA1 (Edg2). Like LPA1 (Edg2), LPA2 (Edg4) also couples G12/13.
Five Edg/S1P receptors have been identified which bind S1P. S1P1 (Edg1), S1P3 (Edg3), S1P2 (Edg5), S1P4 (Edg6) and S1P5 (Edg8) couple to multiple types of G proteins and mediate effects through ras and MAP kinase, rho, phospholipase C (PLC), and protein tyrosine kinases. S1P1 (Edg1) is widely expressed in most tissues. On binding S1P, S1P1 (Edg1) couples to G protein Gi/o, and mediates activation of Ras-MAP Kinase, Ca2+ mobilization, activation of PLC, and inhibition of adenylate cyclase (5). Loss of the receptor affects a wide range of processes including angiogenesis, neurogenesis, embryonic development and lymphocyte trafficking (4).
S1P2 (Edg5) and S1P3 (Edg3) are widely expressed in most tissues in adults and some embryonic tissues. On binding S1P, S1P2 (Edg5) can couple G-proteins Gi/o, Gs, Gq and G12/13 and is involved in cell proliferation and motility. Deletion of the S1P2 (Edg5) gene has been linked to cellular defects affecting hair cells, defects in vascularization and promotes angiogenesis in pathological conditions (4). S1P3 (Edg3) can couple Gi/o, Gq and G12/13, on binding S1P, but predominantly couples Gq leading to an increase in [Ca2+]i and PLC. Studies suggest that S1P3 (Edg3) regulates a variety of cell types and biological processes including regulating lymphoid endothelial cells, endothelial progenitor cells, myocardial perfusion and regulation of heart rate in rodents. (4).
S1P4 (Edg6) is primarily expressed in lymphoid tissue (6) and couples G-protein Gs, Gq and G12/13. S1P5 (Edg8) is expressed in the brain and spleen tissue and can couple G-proteins Gs, Gq and G12/13. Deletion of S1P5 (Edg8) is reported to affect the trafficking of natural killer cells.
The following is a list of S1P and LPA receptor products available from Exalpha:
|EDGSP||EDG Sample Pack (20ug each) (DISCONTINUED)||1 EA|
|c175ms||EDG-3, N terminal (DISCONTINUED) Monoclonal Antibody||50 µg|
|c185ms||EDG-5, N terminal (DISCONTINUED) Monoclonal Antibody||50 µg|
|X1093PS||EDG1 (S1P1) (C Terminal) Polyclonal Antibody||50 µg|
|c174ps||EDG2, C terminal Polyclonal Antibody||50 µg|
|c175m||EDG3 (S1P3) (N Terminal) DISCONTINUED Monoclonal Antibody||100 µg|
|c176ms||EDG3, C terminal (DISCONTINUED) Monoclonal Antibody||50 µg|
|X1225B||EDG4 (LPA2) (N Terminal) Blocking Peptide||50 µg|
|c180m||EDG4 (LPA2), N terminal (DISCONTINUED) Monoclonal Antibody||100 µg|
|c181m||EDG4 (LPA2), C terminal (DISCONTINUED) Monoclonal Antibody||100 µg|
|c181ms||EDG4 (LPA2), C terminal (DISCONTINUED) Monoclonal Antibody||50 µg|
|c180ms||EDG4 (LPA2), N terminal (DISCONTINUED) Monoclonal Antibody||50 µg|
|X1534B||EDG6 (S1P4), C terminal (Replace with X1312B) Blocking Peptide||50 µg|
|X1094PS||EDG8 (S1P5), C terminal (DISCONTINUED) Polyclonal Antibody||50 µg|
|X1570P||Lysophosphatidic Acid 2 (LPA2) Receptor (EDG4) CT Polyclonal Antibody||100 µg|
|X1652P||Lysophosphatidic Acid Acetyltransferse beta Antigen Immunoaffinity Purified Polyclonal||100 µg|
|X1218C||Lysophosphatidic Acid Receptor 1 (EDG2) Control Lysate||100 µl|
|X1274MP||Lysophosphatidic Acid Receptor 1 (EDG2) Membrane Preparation||50 Tests|
|c174p||Lysophosphatidic Acid Receptor 1 CT (EDG-2) Polyclonal Antibody||100 µg|
|X1269B||Lysophosphatidic Acid Receptor 1 CT (EDG-2) Blocking Peptide||50 µg|
|X1219C||Lysophosphatidic Acid Receptor 2 (EDG-4) Control Lysate||100 µl|
|X1546MP||Lysophosphatidic Acid Receptor 2 (EDG-4) Membrane Preparation||50 Tests|
|X1573B||Lysophosphatidic Acid Receptor 2 (EDG4) CT Blocking Peptide||50 µg|
|X1220C||Lysophosphatidic Acid Receptor 3 (EDG-7) Control Lysate||100 µl|
|X1275MP||Lysophosphatidic Acid Receptor 3 (EDG-7) Membrane Preparation||50 Tests|
|X1183P||Lysophosphatidic Acid Receptor 3 CT (EDG-7) Polyclonal Antibody||100 µg|
|X1227B||Lysophosphatidic Acid Receptor 3 CT (EDG-7) Blocking Peptide||50 µg|
|X1217C||Sphingosine 1 Phosphate Receptor 1 (EDG-1) Control Lysate||100 µl|
|X1273MP||Sphingosine 1 Phosphate Receptor 1 (EDG-1) Membrane Preparation||50 Tests|
|X1093P||Sphingosine 1 Phosphate Receptor 1 (EDG-1) CT Polyclonal Antibody||100 µg|
|X1224B||Sphingosine 1 Phosphate Receptor 1 (EDG-1) CT Blocking Peptide||50 µg|
|X1094P||Sphingosine 1 Phosphate Receptor 5 CT (EDG-8) Polyclonal Antibody||100 µg|
|X1228B||Sphingosine 1 Phosphate Receptor 5 CT (EDG-8) Blocking Peptide||50 µg|
|X1589P||Sphingosine 1 Phosphate 3 Receptor (EDG-3) CT Polyclonal Antibody||100 µg|
|X1690B||Sphingosine 1 Phosphate 3 Receptor (EDG-3) CT Blocking Peptide||50 µg|
|X1590P||Sphingosine 1 Phosphate 3 Receptor (EDG-3) NT Polyclonal Antibody||100 µg|
|X1182P||Sphingosine 1 Phosphate 4 Receptor (CT) (EDG6) Polyclonal Antibody||100 µg|
|X1311C||Sphingosine 1 Phosphate 4 Receptor (CT) (EDG6) Control Lysate||100 µl|
|X1312B||Sphingosine 1 Phosphate 4 Receptor (CT) (EDG6) Blocking Peptide||50 µg|
|X1533M||Sphingosine 1 Phosphate 4 Receptor (CT) (EDG6) Monoclonal Antibody||100 µg|
|X2786M||Sphingosine 1 Phosphate 4 Receptor (CT) (EDG6) Alexa647 Conjugate Monoclonal Antibody||100 µg|
|X1626M||Sphingosine 1 Phosphate 4 Receptor (CT) (EDG6) FITC Conjugate Monoclonal Antibody||100 µg|
|X1487C||Sphingosine 1 Phosphate 4 Receptor (EDG8) Control Lysate||100 µl|
|X1592P||Sphingosine 1 Phosphate 4 Receptor (IN) (EDG6) Polyclonal Antibody||100 µg|
|X2717B||Sphingosine 1 Phosphate 4 Receptor (NT) (EDG6) Blocking Peptide||50 µg|
|X1593P||Sphingosine 1 Phosphate 4 Receptor (NT) (EDG6) NT Polyclonal Antibody||100 µg|
|X1547MP||Sphingosine 1 Phosphate Receptor 4 (EDG6) Membrane Preparation||50 Tests|
|X1631P||Sphingosine 1-Phosphate Lyase 1 Antigen Immunoaffinity Purified Polyclonal||100 µg|
|X1643B||Sphingosine 1-Phosphate Lyase 1 Blocking Peptide Blocking Peptide||50 µg|
|X1636P||Sphingosine 1-Phosphate Phosphatase 1 Polyclonal Antibody||100 µg|
|X1644B||Sphingosine 1-Phosphate Phosphatase 1 Blocking Peptide||50 µg|
|X1637P||Sphingosine 1-Phosphate Phosphatase 2 Antigen Immunoaffinity Purified Polyclonal||100 µg|
|X1645B||Sphingosine 1-Phosphate Phosphatase 2 Blocking Peptide||50 µg|
|X1627P||Sphingosine Kinase 1 Polyclonal Antibody||100 µg|
|X2155P||Sphingosine Kinase 1 Antigen Immunoaffinity Purified Polyclonal||50 µg|
|X2156P||Sphingosine Kinase 1 Antigen Immunoaffinity Purified Polyclonal||50 µg|
|X1632B||Sphingosine Kinase 1 Blocking Peptide Blocking Peptide||50 µg|
|X1877B||Phospho Sphingosine Kinase 1 (Ser225), Mouse Blocking Peptide||50 µg|
|X1875B||Sphingosine Kinase 1, Long Form, Rat Blocking Peptide||50 µg|
|X2038P||Sphingosine Kinase 1, Long Form, Rat Polyclonal Antibody||100 µg|
|X1848P||Sphingosine Kinase 1, Long Form, Rat Reactive Antigen Immunoaffinity Purified Polyclonal||100 µg|
|X1878B||Sphingosine Kinase 1, Mouse Blocking Peptide||50 µg|
|X1882P||Sphingosine Kinase 1, Mouse Antigen Immunoaffinity Purified Polyclonal||50 µg|
|X1849P||phospho-Sphingosine Kinase 1,(pS225), Mouse Reactive Antigen Immunoaffinity Purified Polyclonal||100 µg|
|X1628P||Sphingosine Kinase 2 Antigen Immunoaffinity Purified Polyclonal||100 µg|
|X1642B||Sphingosine Kinase 2 Blocking Peptide Blocking Peptide||50 µg|
|X1775P||Sphingosine Kinase 2, Long Form Polyclonal Antibody||100 µg|
|X1880P||Sphingosine Kinase 2, Long Form, Human Antigen Immunoaffinity Purified Polyclonal||100 µg|
|X1881B||Sphingosine Kinase 2, Long Form, Human Blocking Peptide||50 µg|
- Moolenaar, WH (1995). Lysophosphatidic acid, a multifunctional phospholipid messenger. J Biol Chem.270(22):12949-52.
- Mendelson, K et al (2014). Sphingosine 1-phosphate signalling. Development.141(1): 5–9.
- Maceyka, M et al (2012) Sphingosine 1-phosphate signalling and its role in disease. Trends Cell Biol. 22(1): 50–60.
- Chun, J et al (2010). International Union of Basic and Clinical Pharmacology. LXXVIII. Lysophospholipid receptor nomenclature. Pharmacol Rev.62(4):579-87.
- Okamoto, H et al (1998). S1P1 (EDG1) is a functional sphingosine-1-phosphate receptor that is linked via a Gi/o to multiple signaling pathways, including phospholipase C activation, Ca2+ mobilization, Ras-mitogen-activated protein kinase activation, and adenylate cyclase inhibition. J Biol Chem. 273(42):27104-10.
- Gräler MH, Bernhardt G, Lipp M. (1998). EDG6, a novel G-protein-coupled receptor related to receptors for bioactive lysophospholipids, is specifically expressed in lymphoid tissue. Genomics. 53(2):164-9.