論文 - 詳細
| RRC ID | 42865 |
|---|---|
| 著者 | de Gorter DJ, Vos JC, Pals ST, Spaargaren M. |
| タイトル | The B cell antigen receptor controls AP-1 and NFAT activity through Ras-mediated activation of Ral. |
| ジャーナル | J Immunol |
| Abstract |
Signaling by the BCR involves activation of several members of the Ras superfamily of small GTPases, among which is Ras itself. Ras can control the activity of multiple effectors, including Raf, PI3K, and guanine nucleotide exchange factors for the small GTPase Ral. Ras, Raf, and PI3K have been implicated in a variety of processes underlying B cell development, differentiation, and function; however, the role of Ral in B lymphocytes remains to be established. In this study, we show that Ral is activated upon BCR stimulation in human tonsillar and mouse splenic B lymphocytes and in B cell lines. Using signaling molecule-deficient B cells, we demonstrate that this activation is mediated by Lyn and Syk, Btk, phospholipase C-gamma2, and inositol-1,4,5-trisphosphate receptor-mediated Ca(2+) release. In addition, although Ral can be activated by Ras-independent mechanisms, we demonstrate that BCR-controlled activation of Ral is dependent on Ras. By means of expression of the dominant-negative mutants RasN17 and RalN28, or of RalBPDeltaGAP, a Ral effector mutant which sequesters active Ral, we show that Ras and Ral mediate BCR-controlled transcription of c-fos. Furthermore, while not involved in NF-kappaB activation, Ras and Ral mediate BCR-controlled activation of JUN/ATF2 and NFAT transcription factors. Taken together, our data show that Ral is activated upon BCR stimulation and mediates BCR-controlled activation of AP-1 and NFAT transcription factors. These findings suggest that Ral plays an important role in B cell development and function. |
| 巻・号 | 178(3) |
| ページ | 1405-14 |
| 公開日 | 2007-2-1 |
| DOI | 10.4049/jimmunol.178.3.1405 |
| PII | 178/3/1405 |
| PMID | 17237388 |
| MeSH | B-Lymphocytes / cytology B-Lymphocytes / physiology Cell Line, Tumor Cells, Cultured Humans Mutation NFATC Transcription Factors / metabolism* Palatine Tonsil / cytology Receptors, Antigen, B-Cell / physiology* Transcription Factor AP-1 / metabolism* ral GTP-Binding Proteins / genetics ral GTP-Binding Proteins / metabolism* ras Proteins / metabolism* |
| IF | 4.886 |
| 引用数 | 19 |
| WOS 分野 | IMMUNOLOGY |
| 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 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| ヒト・動物細胞 | Lyn^(-)/Syk^(-) DT40(RCB1500) Btk^(-) DT40(RCB1468) PLC-γ2^(-) DT40(RCB1469) |