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Cited by 810Sphingolipid Metabolism and SignalingLysosomal Storage Disorders ResearchProtein Kinase Regulation and GTPase Signaling

The outs and the ins of sphingosine-1-phosphate in immunity

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Spiegel, Sarah, Milstien, Sheldon·2011·Nature Reviews Immunology
DOI 10.1038/nri2974PMC PMC3368251
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Abstract

The potent lipid mediator sphingosine-1-phosphate (S1P) is produced inside cells by two closely related kinases, sphingosine kinase 1 (SPHK1) and SPHK2, and has emerged as a crucial regulator of immunity. Many of the actions of S1P in innate and adaptive immunity are mediated by its binding to five G protein-coupled receptors, designated S1PR1-5, but recent findings have also identified important roles for S1P as a second messenger during inflammation. In this Review, we discuss recent advances in our understanding of the roles of S1P receptors and describe the newly identified intracellular targets of S1P that are crucial for immune responses. Finally, we discuss the therapeutic potential of new drugs that target S1P signalling and functions.

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  • S1P mainly functions as an extracellular ligand for G protein-coupled receptors and as a transcriptional regulator in the nucleus.

    “S1P, a product of SphK2, mainly functions as an extracellular ligand for G protein-coupled receptors and as a transcriptional regulator in the nucleus (49).”

    From Nuclear SphK2/S1P signaling is a key regulator of ApoE production and Aβ uptake in astrocytes (2024) · cites this paper as [49]

    The Abstract describes S1P as an agonist of G protein-coupled S1P receptors, and “Regulation of histone deacetylases by S1P” describes nuclear S1P produced by SPHK2 influencing transcription through HDAC1 and HDAC2. The paper also describes other intracellular actions, including regulation of TNFR signalling, so it does not establish that the two functions named are S1P’s main functions. Page numbers were not provided in our copy. (LLM, conf=0.82)

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Authors
Spiegel, S., & Milstien, S.
Affiliations
Virginia Commonwealth University (US)
Corresponding author
Spiegel, Sarah
ORCID
Venue
Nature Reviews Immunology
Publisher
Springer Science and Business Media LLC
Published
2011-05-06
Volume
11
Issue
6
Pages
403-415
ISSN
  • 1474-1733 (ISSN-L)
  • 1474-1741
DOI
10.1038/nri2974
PMC
PMC3368251
OpenAlex
W2076738925
Cited by
810
References
2
Citations by year
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FWCI
5.71
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature reviews. Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Cancer Institute (R01CA061774)
  • National Institute of General Medical Sciences (R01GM043880, R37GM043880)
  • National Institute of Allergy and Infectious Diseases (U19AI077435, R01AI050094)
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, sphingosine kinase 1, sphingosine kinase 2, G protein-coupled receptors, lymphocyte migration, innate immunity, adaptive immunity, inflammation, second messengers
MeSH terms
Sphingosine-1-Phosphate Receptors, Sphingosine Kinase, Animals, Humans, Immunity, Inflammation, Lysophospholipids, Sphingosine, Second Messenger Systems, Phosphotransferases (Alcohol Group Acceptor), Models, Immunological, Receptors, Lysosphingolipid

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