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Cited by 425Sphingolipid Metabolism and SignalingLysosomal Storage Disorders ResearchProtein Kinase Regulation and GTPase Signaling

Sphingosine 1-Phosphate Receptor Signaling

Rosen, Hugh, Gonzalez-Cabrera, Pedro J., Sanna, M. Germana, Brown, Steven·2009·Annual Review of Biochemistry
DOI 10.1146/annurev.biochem.78.072407.103733
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Abstract

The sphingosine 1-phosphate (S1P) receptor signaling system is a productive model system. A hydrophobic zwitterionic lysophospholipid ligand with difficult physical properties interacts with five high-affinity G protein–coupled receptors to generate multiple downstream signals. These signals modulate homeostasis and pathology on a steep agonist concentration-response curve. Ligand presence is essential for vascular development and endothelial integrity, while acute increases in ligand concentrations result in cardiac death. Understanding this integrated biochemical system has exemplified the impact of both genetics and chemistry. Developing specific tools with defined biochemical properties for the reversible modulation of signals in real time has been essential to complement insights gained from genetic approaches that may be irreversible and compensated. Despite its knife-edge between life and death, this system, based in part on receptor subtype-selectivity and in part on differential attenuation of deleterious signals, now appears to be on the cusp of meaningful therapy for multiple sclerosis.

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Crossref · 10.1146/annurev.biochem.78.072407.103733

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151 of 151 references verified0 citation errors · 0 not checkable

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  • Primary bile acids exert direct negative myocardial chronotropic effects in a dose-dependent fashion.

    “Early studies of primary bile acids have been shown to exert direct negative myocardial chronotropic effects in a dose-dependent fashion132,133.”

    From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [132]

  • Secondary bile acids can also exert similar negative chronotropic effects, though at lower concentrations relative to primary bile acids even in cholestatic states.

    “Though at lower concentrations relative to primary bile acids even in cholestatic states, secondary bile acids can also exert similar effects.”

    From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [132]

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Authors
Rosen, H., Gonzalez-Cabrera, P. J., Sanna, M. G., & Brown, S.
Affiliations
  • Scripps Research Institute (US)
  • Departments of Chemical Physiology and Immunology and The Scripps Research Institute Molecular Screening Center, The Scripps Research Institute, La Jolla, California 92037;
ORCID
Venue
Annual Review of Biochemistry
Publisher
Annual Reviews
Published
2009-06-01
Volume
78
Issue
1
Pages
743-768
ISSN
  • 0066-4154 (ISSN-L)
  • 1545-4509
DOI
10.1146/annurev.biochem.78.072407.103733
OpenAlex
W2127032203
Cited by
404
References
151
Citations by year
2026: 1 · 2025: 8 · 2024: 8 · 2023: 10 · 2022: 12 · 2021: 19 · 2020: 17 · 2019: 18 · 2018: 29 · 2017: 27 · 2016: 28 · 2015: 21 · 2014: 27 · 2013: 48 · 2012: 50
FWCI
3.46
Type
journal article
Language
en
Open access
closed
Locations
  • Annual Review of Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
sphingosine-1-phosphate, S1P receptors, G protein-coupled receptors, receptor signaling, vascular development, endothelial integrity, cardiovascular mortality, signal attenuation, receptor subtype selectivity, multiple sclerosis treatment
MeSH terms
Animals, Cardiovascular System, Humans, Lymphoid Tissue, Multiple Sclerosis, Signal Transduction, Receptors, Lysosphingolipid

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