論文 - 詳細
| RRC ID | 19641 |
|---|---|
| 著者 | Fukumoto T, Kubota Y, Kitanaka A, Yamaoka G, Ohara-Waki F, Imataki O, Ohnishi H, Ishida T, Tanaka T. |
| タイトル | Gab1 transduces PI3K-mediated erythropoietin signals to the Erk pathway and regulates erythropoietin-dependent proliferation and survival of erythroid cells. |
| ジャーナル | Cell Signal |
| Abstract |
In this study, we examined the biological functions of Gab1 in erythropoietin receptor (EPOR)-mediated signaling in vivo. Knockdown of Gab1 by the introduction of the Gab1 siRNA expression vector into F-36P human erythroleukemia (F-36P-Gab1-siRNA) cells resulted in a reduction of cell proliferation and survival in response to EPO. EPO-induced activation of Erk1/2 but not of Akt was significantly suppressed in F-36P-Gab1-siRNA cells compared with mock-transfected F-36P cells. The co-immunoprecipitation experiments revealed an EPO-enhanced association of Gab1 with the Grb2-SOS1 complex and SHP-2 in F-36P cells. A selective inhibitor of phosphatidylinositol 3-kinase (PI3K) LY294002 and short interfering RNA (siRNA) duplexes targeting the p85 regulatory subunit of PI3K (p85-siRNA) independently suppressed tyrosine phosphorylation of Gab1; its association with Grb2, SHP-2 and p85; and the activation of Erk in EPO-treated F-36P cells. LY294002 inhibited EPO-induced tyrosine phosphorylation of Gab1 and its association with Grb2 in human primary EPO-sensitive erythroid cells. The co-immunoprecipitation experiments using the Jak inhibitor AG490 or siRNA duplexes targeting Jak2 and in vitro binding experiments demonstrated that Jak2 regulated Gab1-mediated Erk activation through tyrosine phosphorylation of Gab1. Taken together, these results suggest that Gab1 couples PI3K-mediated EPO signals with the Ras/Erk pathway and that Gab1 plays an important role in EPOR-mediated signal transduction involved in the proliferation and survival of erythroid cells. |
| 巻・号 | 21(12) |
| ページ | 1775-83 |
| 公開日 | 2009-12-1 |
| DOI | 10.1016/j.cellsig.2009.07.013 |
| PII | S0898-6568(09)00220-4 |
| PMID | 19665053 |
| MeSH | Adaptor Proteins, Signal Transducing / genetics Adaptor Proteins, Signal Transducing / metabolism* Apoptosis Cell Line, Tumor Cell Proliferation Chromones / pharmacology Enzyme Inhibitors / pharmacology Erythroid Cells / cytology* Erythroid Cells / metabolism Erythropoietin / metabolism* GRB2 Adaptor Protein / metabolism Gene Knockdown Techniques Humans Janus Kinase 2 / antagonists & inhibitors Janus Kinase 2 / metabolism Leukemia, Erythroblastic, Acute / metabolism Mitogen-Activated Protein Kinase 1 / metabolism* Mitogen-Activated Protein Kinase 3 / metabolism* Morpholines / pharmacology Phosphatidylinositol 3-Kinases / metabolism* Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism Receptors, Erythropoietin / metabolism SOS1 Protein / metabolism |
| IF | 3.968 |
| 引用数 | 8 |
| WOS 分野 | 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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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | F-36P(RCB0775) |