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Sphingosine 1-Phosphate Receptor Family

Sphingosine 1-phosphate (S1P), a highly active lipid mediator, regulates diverse cellular responses involved in immunity, heart rate, smooth muscle tone, and endothelial barrier function. This phospholipid is abundant in erythrocytes, brain, spleen, and eyes. Signals initiated by S1P are transduced by five S1P receptors, named S1PR1-5. S1P receptors have seven transmembrane segments and are coupled to G-proteins, which transduce their actions. Expression patterns of the five S1PRs vary in tissues and also during development and aging. For instance, S1PR1-3 subtypes are present ubiquitously whereas S1PR4 is expressed in lymphoid tissue and S1PR5 in the spleen and oligodendrocytes.

The S1P signaling system plays essential roles in vascular development and endothelial integrity, control of cardiac rhythm, and routine oral treatment of multiple sclerosis. They are attractive therapeutic targets for several diseases, such as chronic inflammatory pathologies, autoimmunity, and cancer. As a result, several well-characterized agonists and antagonists of S1PRs have been developed, such as FTY720 (oral therapy for relapsing-remitting multiple sclerosis) and SEW2871 (receptor internalization and recycling). Most of these compounds have been directed toward modulating the activity of S1PR1. Novel agonists and antagonists targeting the other S1P receptors remain to be developed in the future. Here, we give an introduction to each of these five receptors regarding the structure, features, functions, recent advances, etc.

Human Sphingosine 1-phosphate Receptor Members
S1PR2 S1PR3 S1PR4 S1PR5

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Sphingosine 1-Phosphate Receptor Family

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