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Sphingosine 1-phosphate signalling in mammalian cells
1Department of Physiology and Pharmacology, Strathclyde Institute for Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 ONR, Scotland, UK. susan.pyne@strath.ac.uk
The Biochemical Journal
|July 6, 2000
Summary
Sphingosine 1-phosphate (S1P) is a lipid mediator involved in cell signaling. This review explores S1P
Area of Science:
- Biochemistry and Molecular Biology
- Cell Signaling
- Pharmacology
Background:
- Sphingosine 1-phosphate (S1P) is a bioactive lysolipid synthesized by sphingosine kinase and degraded via enzymatic cleavage or dephosphorylation.
- S1P mediates cellular responses by binding to the endothelial differentiation gene (EDG) G-protein-coupled receptor family (EDG1, EDG3, EDG5, EDG6, EDG8).
- These receptors activate diverse intracellular signaling pathways, including those involving G proteins, phospholipases, and mitogen-activated protein kinases.
Purpose of the Study:
- To review recent advances in understanding the enzymes involved in sphingosine 1-phosphate metabolism.
- To discuss the receptor-dependent and intracellular actions of sphingosine 1-phosphate.
- To explore the pathophysiological roles of sphingosine 1-phosphate in diseases like cancer and inflammation.
Main Methods:
- Literature review of recent research on sphingosine 1-phosphate metabolism, signaling, and function.
- Analysis of evidence supporting both extracellular receptor-mediated and intracellular roles of sphingosine 1-phosphate.
- Discussion of therapeutic targets and future research directions for sphingosine 1-phosphate.
Main Results:
- Sphingosine 1-phosphate elicits diverse biological responses, including mitogenesis, differentiation, migration, and apoptosis, through receptor-dependent pathways.
- Evidence suggests potential intracellular actions of sphingosine 1-phosphate, such as calcium mobilization and kinase activation.
- Sphingosine 1-phosphate is implicated in pathophysiological conditions, including cancer, angiogenesis, and inflammation.
Conclusions:
- Sphingosine 1-phosphate exhibits a dual role, acting both extracellularly via receptors and potentially intracellularly.
- Further research is needed to fully elucidate the dual signaling and action profile of sphingosine 1-phosphate.
- Targeting sphingosine 1-phosphate pathways offers potential for therapeutic intervention in various diseases.