Cited by 424Sphingolipid Metabolism and SignalingLysosomal Storage Disorders ResearchProtein Kinase Regulation and GTPase Signaling

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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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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: Rosen, Hugh
Sanna, M. Germana
Brown, Steven
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 › Genetics (clinical) › 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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