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Palmitoylation of the sphingosine 1-phosphate receptor S1P1 is involved in its signaling functions and internalization
| Title: | Palmitoylation of the sphingosine 1-phosphate receptor S1P1 is involved in its signaling functions and internalization |
| Authors: | Ohno, Yusuke Browse this author | | Ito, Ayako Browse this author | | Ogata, Ren Browse this author | | Hiraga, Yuki Browse this author | | Igarashi, Yasuyuki Browse this author →KAKEN DB | | Kihara, Akio Browse this author →KAKEN DB |
| Issue Date: | Aug-2009 |
| Publisher: | Wiley-Blackwell |
| Journal Title: | Genes to Cells |
| Volume: | 14 |
| Issue: | 8 |
| Start Page: | 911 |
| End Page: | 923 |
| Publisher DOI: | 10.1111/j.1365-2443.2009.01319.x |
| PMID: | 19619245 |
| Abstract: | The lipid mediator sphingosine 1-phosphate (S1P) regulates several cellular processes through binding to its receptors (S1P1-S1P5), which are heterotrimeric G protein-coupled receptors. Here, we report that all S1P receptors are palmitoylated. In S1P1, three Cys residues in the cytoplasmic tail are palmitoylated. We examined the roles of palmitoylation of S1P1 using model cells in which wild type S1P1 or a non-palmitoylated mutant S1P1 was overproduced. Compared to wild type S1P1, the non-palmitoylated S1P1 exhibited similar binding affinity to the natural ligand S1P but lower affinity to the synthetic ligand FTY720 phosphate (FTY720-P), the active form of the immunomodulator FTY720. However, downstream signaling of non-palmitoylated S1P1 was similarly affected by S1P and FTY720-P stimulation. Moreover, upon stimulation with S1P, internalization of the mutant non-palmitoylated S1P1 was retarded, compared to that of the wild type protein. This effect was much more pronounced with FTY720-P stimulation. Similar differences were observed for the phosphorylation of S1P1 and its mutant. These findings may provide insights into the molecular mechanisms of the pharmacological effects of FTY720. Finally, palmitoylation of wild type S1P1 increased upon treatment with S1P, suggesting that S1P1 undergoes a palmitoylation/depalmitoylation cycle after stimulation by its ligands. |
| Rights: | The definitive version is available at www3.interscience.wiley.com |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/42607 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 木原 章雄
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