ArticleThe Journal of biological chemistry2008
S1P1 receptor localization confers selectivity for Gi-mediated cAMP and contractile responses.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 76 citations in OpenAlex.
- A genetic variant of adenylate cyclase 7 associated with ulcerative colitis shows impaired function and G-protein-coupled receptor signaling.Human genetics · 2026Article
- Suppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases.Nature communications · 2025Article
- Sphingolipid Metabolism and Signalling Pathways in Heart Failure: From Molecular Mechanism to Therapeutic Potential.Journal of inflammation research · 2025Review
- Unique pharmacological properties of etrasimod among S1P receptor modulators.FEBS open bio · 2025Article
- Sphingosine-1-Phosphate Signaling in Cardiovascular Diseases.Biomolecules · 2023Review
- You aren't IMMUNE to the ceramides that accumulate in cardiometabolic disease.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2022Article
- Review
- Opposing Roles of S1PCells · 2020Article
- Combinatorial allosteric modulation of agonist response in a self-interacting G-protein coupled receptor.Communications biology · 2020Article
- Sphingolipids in the Heart: From Cradle to Grave.Frontiers in endocrinology · 2020Review
- Requirement for sphingosine kinase 1 in mediating phase 1 of the hypotensive response to anandamide in the anaesthetised mouse.European journal of pharmacology · 2019Article
- Sphingosine 1 phosphate receptor-1 (S1PR1) signaling protects cardiac function by inhibiting cardiomyocyte autophagy.Journal of geriatric cardiology : JGC · 2018Article
- Bioluminescence imaging of G protein-coupled receptor activation in living mice.Nature communications · 2017Article
- Selective coupling of the S1PJournal of molecular and cellular cardiology · 2017Article
- Sphingosine-1-Phosphate Promotes the Persistence of Activated CD4 T Cells in Inflamed Sites.Frontiers in immunology · 2017Article
- Sphingosine Kinases and Sphingosine 1-Phosphate Receptors: Signaling and Actions in the Cardiovascular System.Frontiers in pharmacology · 2017Review
- Biological Effects of Naturally Occurring Sphingolipids, Uncommon Variants, and Their Analogs.Neuromolecular medicine · 2016Review
- Sphingosine 1-phosphate elicits RhoA-dependent proliferation and MRTF-A mediated gene induction in CPCs.Cellular signalling · 2016Article
- Implication of sphingosin-1-phosphate in cardiovascular regulation.Frontiers in bioscience (Landmark edition) · 2016Review
- Sphingosine-1-Phosphate Receptor 1 Regulates Cardiac Function by Modulating Ca2+ Sensitivity and Na+/H+ Exchange and Mediates Protection by Ischemic Preconditioning.Journal of the American Heart Association · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Adult mouse ventricular myocytes express S1P(1), S1P(2), and S1P(3) receptors. S1P activates Akt and ERK in adult mouse ventricular myocytes through a pertussis toxin-sensitive (G(i/o)-mediated) pathway. Akt and ERK activation by S1P are reduced approximately 30% in S1P(3) and 60% in S1P(2) receptor knock-out myocytes. With combined S1P(2,3) receptor deletion, activation of Akt is abolished and ERK activation is reduced by nearly 90%. Thus the S1P(1) receptor, while present in S1P(2,3) receptor knock-out myocytes, is unable to mediate Akt or ERK activation. In contrast, S1P induces pertussis toxin-sensitive inhibition of isoproterenol-stimulated cAMP accumulation in both WT and S1P(2,3) receptor knock-out myocytes demonstrating that the S1P(1) receptor can functionally couple to G(i). An S1P(1) receptor selective agonist, SEW2871, also decreased cAMP accumulation but failed to activate ERK or Akt. To determine whether localization of the S1P(1) receptor mediates this signaling specificity, methyl-beta-cyclodextrin (MbetaCD) treatment was used to disrupt caveolae. The S1P(1) receptor was concentrated in caveolar fractions, and associated with caveolin-3 and this localization was disrupted by MbetaCD. S1P-mediated activation of ERK or Akt was not diminished but inhibition of cAMP accumulation by S1P and SEW2871 was abolished by MbetaCD treatment. S1P inhibits the positive inotropic response to isoproterenol and this response is also mediated through the S1P(1) receptor and lost following caveolar disruption. Thus localization of S1P(1) receptors to caveolae is required for the ability of this receptor to inhibit adenylyl cyclase and contractility but compromises receptor coupling to Akt and ERK.
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