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首页> 外文期刊>Genes to cells : >Palmitoylation of the sphingosine 1-phosphate receptor S1P is involved in its signaling functions and internalization
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Palmitoylation of the sphingosine 1-phosphate receptor S1P is involved in its signaling functions and internalization

机译：鞘氨醇1-磷酸受体S1P的棕榈酰化与其信号传导功能和内在化有关

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The lipid mediator sphingosine 1-phosphate (S1P) regulates several cellular processes through binding to its receptors (S1P-S1P), which are heterotrimeric G protein-coupled receptors. Here, we report that all S1P receptors are palmitoylated. In S1P, three Cys residues in the cytoplasmic tail are palmitoylated. We examined the roles of palmitoylation of S1P using model cells in which wild-type S1P or a non-palmitoylated mutant S1P was overproduced. Compared with wild-type S1P, the non-palmitoylated S1P exhibited binding affinity similar to the natural ligand S1P but lower to the synthetic ligand FTY720 phosphate (FTY720-P), the active form of the immunomodulator FTY720. However, downstream signaling of non-palmitoylated S1P was similarly affected by S1P and FTY720-P stimulation. Moreover, upon stimulation with S1P, internalization of the mutant non-palmitoylated S1P was retarded, compared with that of the wild-type protein. This effect was much more pronounced with FTY720-P stimulation. Similar differences were observed for the phosphorylation of S1P and its mutant. These findings may provide insights into the molecular mechanisms of the pharmacological effects of FTY720. Finally, palmitoylation of wild-type S1P increased upon treatment with S1P, suggesting that S1P undergoes a palmitoylation/depalmitoylation cycle after stimulation by its ligands.
机译：脂质介导的鞘氨醇1-磷酸（S1P）通过与受体（S1P-S1P）结合而调节多个细胞过程，该受体是异源三聚G蛋白偶联受体。在这里，我们报告所有S1P受体都被棕榈酰化。在S1P中，胞质尾中的三个Cys残基被棕榈酰化。我们检查了使用野生型S1P或非棕榈酰化突变体S1P过量生产的模型细胞对S1P进行棕榈酰化的作用。与野生型S1P相比，非棕榈酰化的S1P表现出与天然配体S1P相似的结合亲和力，但低于合成配体FTY720磷酸酯（FTY720-P），即免疫调节剂FTY720的活性形式。但是，非棕榈酰化的S1P的下游信号传递同样受到S1P和FTY720-P刺激的影响。此外，与野生型蛋白相比，在用S1P刺激后，突变体非棕榈酰化S1P的内在化受到了阻碍。 FTY720-P刺激更明显。对于S1P及其突变体的磷酸化观察到相似的差异。这些发现可能提供有关FTY720药理作用的分子机制的见解。最后，野生型S1P的棕榈酰化在用S1P处理后增加，表明S1P在其配体刺激后经历了棕榈酰化/去棕榈酰化循环。

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