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Cited by 1,039Sphingolipid Metabolism and SignalingLysosomal Storage Disorders ResearchProtein Kinase Regulation and GTPase Signaling

Sphingosine-1-phosphate signaling and its role in disease

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Maceyka, Michael, Harikumar, Kuzhuvelil B., Milstien, Sheldon, Spiegel, Sarah·2012·Trends in Cell Biology
DOI 10.1016/j.tcb.2011.09.003PMC PMC3253987
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Abstract

The bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P) is now recognized as a critical regulator of many physiological and pathophysiological processes, including cancer, atherosclerosis, diabetes and osteoporosis. S1P is produced in cells by two sphingosine kinase isoenzymes, SphK1 and SphK2. Many cells secrete S1P, which can then act in an autocrine or paracrine manner. Most of the known actions of S1P are mediated by a family of five specific G protein-coupled receptors. More recently, it was shown that S1P also has important intracellular targets involved in inflammation, cancer and Alzheimer's disease. This suggests that S1P actions are much more complex than previously thought, with important ramifications for development of therapeutics. This review highlights recent advances in our understanding of the mechanisms of action of S1P and its roles in disease.

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  • Inflammatory cytokines and ROS are implicated in pathophysiology of hypoxia and psychiatric disorders.

    “Moreover, inflammatory cytokines and ROS are known to activate sphingosine 1 phosphate and are implicated in pathophysiology of hypoxia and psychiatric disorders (49, 52).”

    From Mechanistic inferences on metabolic dysfunction in posttraumatic stress disorder from an integrated model and multiomic analysis: role of glucocorticoid receptor sensitivity (2019) · cites this paper as [49]

    The “Localized production of S1P” section says pro-inflammatory cytokines activate sphingosine kinase 1, an enzyme involved in S1P production. It does not establish that ROS activate S1P or that inflammatory cytokines and ROS contribute to the pathophysiology of hypoxia or psychiatric disorders. Searches for those terms found no supporting passage in our copy; page numbers were unavailable. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • Inflammatory cytokines and ROS activate sphingosine 1 phosphate.

    “Moreover, inflammatory cytokines and ROS are known to activate sphingosine 1 phosphate and are implicated in pathophysiology of hypoxia and psychiatric disorders (49, 52).”

    From Mechanistic inferences on metabolic dysfunction in posttraumatic stress disorder from an integrated model and multiomic analysis: role of glucocorticoid receptor sensitivity (2019) · cites this paper as [49]

    The “Localized production of S1P” section says pro-inflammatory cytokines activate sphingosine kinase 1, which produces S1P; it does not say they directly activate S1P. No passage found says ROS activates S1P, or links this mechanism to hypoxia or psychiatric disorders (pages unavailable in our copy). (LLM, conf=0.86)

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Research works printed but not linked: 100

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Cited by

Sorted by citations

Authors
Maceyka, M., Harikumar, K. B., Milstien, S., & Spiegel, S.
Affiliations
Virginia Commonwealth University (US)
Corresponding author
Spiegel, Sarah
ORCID
Venue
Trends in Cell Biology
Publisher
Elsevier BV
Published
2012-01
Volume
22
Issue
1
Pages
50-60
ISSN
0962-8924 (ISSN-L)
DOI
10.1016/j.tcb.2011.09.003
PMC
PMC3253987
OpenAlex
W2034607874
Cited by
1,039
References
3
Citations by year
2026: 40 · 2025: 58 · 2024: 53 · 2023: 48 · 2022: 61 · 2021: 87 · 2020: 105 · 2019: 94 · 2018: 81 · 2017: 90 · 2016: 71 · 2015: 69 · 2014: 70 · 2013: 75 · 2012: 34
FWCI
5.25
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Trends in Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Cancer Institute (R01CA-61774, R01CA061774)
  • National Institute of General Medical Sciences (R37GM043880)
  • National Institute of Allergy and Infectious Diseases (R01AI50094, 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 signaling, sphingosine kinase, sphingosine kinase 1, sphingosine kinase 2, G protein-coupled receptors, autocrine and paracrine signaling, inflammation, cancer, atherosclerosis, diabetes mellitus, osteoporosis, Alzheimer's disease, therapeutics
MeSH terms
Sphingosine Kinase, Animals, Biological Transport, Humans, Lysophospholipids, Sphingosine, Signal Transduction, Phosphotransferases (Alcohol Group Acceptor)

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