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Updated: Feb 19, 2026

A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors
Published on: June 8, 2022
Sphingosine Kinases/Sphingosine 1-Phosphate Signaling in Hepatic Lipid Metabolism
Eric K Kwong1, Xiaojiaoyang Li1, Phillip B Hylemon1
1Department of Microbiology and Immunology, Medical College of Virginia Campus, McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, Virginia, 23298.
Abstract:
The ever-increasing prevalence of metabolic diseases such as dyslipidemia and diabetes in the western world continues to be of great public health concern. Biologically active sphingolipids, such as sphingosine 1-phosphate (S1P) and ceramide, are important regulators of lipid metabolism. S1P not only directly functions as an active intracellular mediator, but also activates multiple signaling pathways via five transmembrane G-protein coupled receptors (GPCRs), S1PR1-5. S1P is exclusively formed by sphingosine kinases (SphKs). Two isoforms of SphKs, SphK1 and SphK2, have been identified. Recent identification of the conjugated bile acid-induced activation of S1PR2 as a key regulator of SphK2 opened new directions for both the sphingolipid and bile acid research fields. The role of SphKs/S1P-mediated signaling pathways in health and various human diseases has been extensively reviewed elsewhere. This review focuses on recent findings related to SphKs/S1P-medaited signaling pathways in regulating hepatic lipid metabolism.
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