論文 - 詳細
| RRC ID | 39633 |
|---|---|
| 著者 | Okamoto H, Takuwa N, Yokomizo T, Sugimoto N, Sakurada S, Shigematsu H, Takuwa Y. |
| タイトル | Inhibitory regulation of Rac activation, membrane ruffling, and cell migration by the G protein-coupled sphingosine-1-phosphate receptor EDG5 but not EDG1 or EDG3. |
| ジャーナル | Mol Cell Biol |
| Abstract |
Sphingosine-1-phosphate (S1P) is a bioactive lysophospholipid that induces a variety of biological responses in diverse cell types. Many, if not all, of these responses are mediated by members of the EDG (endothelial differentiation gene) family G protein-coupled receptors EDG1, EDG3, and EDG5 (AGR16). Among prominent activities of S1P is the regulation of cell motility; S1P stimulates or inhibits cell motility depending on cell types. In the present study, we provide evidence for EDG subtype-specific, contrasting regulation of cell motility and cellular Rac activity. In CHO cells expressing EDG1 or EDG3 (EDG1 cells or EDG3 cells, respectively) S1P as well as insulin-like growth factor I (IGF I) induced chemotaxis and membrane ruffling in phosphoinositide (PI) 3-kinase- and Rac-dependent manners. Both S1P and IGF I induced a biphasic increase in the amount of the GTP-bound active form of Rac. In CHO cells expressing EDG5 (EDG5 cells), IGF I similarly stimulated cell migration; however, in contrast to what was found for EDG1 and EDG3 cells, S1P did not stimulate migration but totally abolished IGF I-directed chemotaxis and membrane ruffling, in a manner dependent on a concentration gradient of S1P. In EDG5 cells, S1P stimulated PI 3-kinase activity as it did in EDG1 cells but inhibited the basal Rac activity and totally abolished IGF I-induced Rac activation, which involved stimulation of Rac-GTPase-activating protein activity rather than inhibition of Rac-guanine nucleotide exchange activity. S1P induced comparable increases in the amounts of GTP-RhoA in EDG3 and EDG5 cells. Neither S1P nor IGF I increased the amount of GTP-bound Cdc42. However, expression of N(17)-Cdc42, but not N(19)-RhoA, suppressed S1P- and IGF I-directed chemotaxis, suggesting a requirement for basal Cdc42 activity for chemotaxis. Taken together, the present results demonstrate that EDG5 is the first example of a hitherto-unrecognized type of receptors that negatively regulate Rac activity, thereby inhibiting cell migration and membrane ruffling. |
| 巻・号 | 20(24) |
| ページ | 9247-61 |
| 公開日 | 2000-12-1 |
| DOI | 10.1128/MCB.20.24.9247-9261.2000 |
| PMID | 11094076 |
| PMC | PMC102182 |
| MeSH | 3T3 Cells Animals CHO Cells Cell Membrane / metabolism* Cell Membrane / ultrastructure Chemotaxis / drug effects* Cricetinae DNA-Binding Proteins / metabolism Humans I-kappa B Proteins* Immediate-Early Proteins / metabolism Insulin-Like Growth Factor I / pharmacology Lysophospholipids* Mice NF-KappaB Inhibitor alpha Phosphatidylinositol 3-Kinases / metabolism Protein Isoforms / metabolism Protein Kinase Inhibitors Protein Serine-Threonine Kinases / metabolism Receptors, Cell Surface / metabolism* Receptors, G-Protein-Coupled* Receptors, Lysophospholipid Recombinant Proteins / genetics Recombinant Proteins / metabolism Signal Transduction* Sphingosine / analogs & derivatives* Sphingosine / metabolism Sphingosine / pharmacology* Stress Fibers / metabolism Transfection cdc42 GTP-Binding Protein / metabolism p21-Activated Kinases rac GTP-Binding Proteins / antagonists & inhibitors* rac GTP-Binding Proteins / metabolism rho GTP-Binding Proteins / metabolism |
| IF | 3.611 |
| 引用数 | 272 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | CHO-K1(RCB0285) |