論文 - 詳細
| RRC ID | 43275 |
|---|---|
| 著者 | Jacob M, Todd L, Sampson MF, Puré E. |
| タイトル | Dual role of Cbl links critical events in BCR endocytosis. |
| ジャーナル | Int Immunol |
| Abstract |
Receptor endocytosis down-regulates ligand-induced signaling in a timely manner and depends on cytoskeletal remodeling. In B lymphocytes, internalization of B cell receptors (BCRs) is also critical to antigen presentation. However, the mechanisms underlying BCR endocytosis are not fully understood. Similarly, the molecular mechanisms linking endocytosis to cytoskeletal remodeling remain poorly defined. We used flow cytometry, pull-down assays, immunochemistry and fluorescence microscopy to investigate BCR internalization in the DT40 B cell line. We demonstrate that ablation of Cbl impacts BCR endocytosis and the underlying cytoskeletal dynamics. Specifically, we demonstrate that ligand-induced endocytosis is impaired in Cbl-/- cells and that the ubiquitin ligase activity is required for Cbl to promote endocytosis. We also show that phosphorylation of CrkII, activation of Rac downstream of CrkII and BCR capping require Cbl. Furthermore, we show that the association of Cbl and CrkII requires phosphorylation of Cbl, but not its ubiquitin ligase activity. Our data indicate that Cbl promotes BCR endocytosis and attenuates ligand-induced signaling by virtue of its ability to orchestrate receptor ubiquitylation and cytoskeletal dynamics. |
| 巻・号 | 20(4) |
| ページ | 485-97 |
| 公開日 | 2008-4-1 |
| DOI | 10.1093/intimm/dxn010 |
| PII | dxn010 |
| PMID | 18283045 |
| MeSH | Actins / metabolism Animals Antibodies / metabolism B-Lymphocytes / immunology* Cell Line Chickens Cytoskeleton / immunology Down-Regulation / immunology Endocytosis / immunology* Humans Ligands Phosphorylation Protein Structure, Tertiary / physiology Proto-Oncogene Proteins c-cbl / deficiency Proto-Oncogene Proteins c-cbl / physiology* Proto-Oncogene Proteins c-crk / metabolism Receptors, Antigen, B-Cell / metabolism* Signal Transduction / immunology Ubiquitin-Protein Ligases / metabolism rac GTP-Binding Proteins / metabolism |
| IF | 3.519 |
| 引用数 | 12 |
| 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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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | |