論文 - 詳細
| RRC ID | 18711 |
|---|---|
| 著者 | Hakozaki A, Yoda M, Tohmonda T, Furukawa M, Hikata T, Uchikawa S, Takaishi H, Matsumoto M, Chiba K, Horiuchi K, Toyama Y. |
| タイトル | Receptor activator of NF-kappaB (RANK) ligand induces ectodomain shedding of RANK in murine RAW264.7 macrophages. |
| ジャーナル | J Immunol |
| Abstract |
Osteoclastogenesis is a highly sophisticated process that involves a variety of membrane-bound proteins expressed in osteoblasts and osteoclast precursors. Over the past several years, proteolytic cleavage and release of the ectodomain of membrane-bound proteins, also referred to as ectodomain shedding, has emerged as an important posttranslational regulatory mechanism for modifying the function of cell surface proteins. In line with this notion, several membrane-bound molecules involved in osteoclastogenesis, including CSF-1R and receptor activator of NF-kappaB ligand (RANKL), are proteolytically cleaved and released from the cell surface. In this study, we investigated whether receptor activator of NF-kappaB (RANK), one of the most essential molecules in osteoclastogenesis, undergoes ectodomain shedding. The results showed that RANK is released in the form of a soluble monomeric protein and that TNF-alpha-converting enzyme is involved in this activity. We also identified potential cleavage sites in the juxtamembrane domain of RANK and found that rRANKL induces RANK shedding in a macrophage-like cell line RAW264.7 via TNFR-associated factor 6 and MAPK pathways. Furthermore, we found that RANKL-induced osteoclastogenesis is accelerated in TNF-alpha-converting enzyme-deficient osteoclast precursors. These observations suggest the potential involvement of ectodomain shedding in the regulation of RANK functions and may provide novel insights into the mechanisms of osteoclastogenesis. |
| 巻・号 | 184(5) |
| ページ | 2442-8 |
| 公開日 | 2010-3-1 |
| DOI | 10.4049/jimmunol.0901188 |
| PII | jimmunol.0901188 |
| PMID | 20118276 |
| MeSH | ADAM Proteins / deficiency ADAM Proteins / genetics ADAM Proteins / metabolism* ADAM17 Protein Animals Binding Sites Blotting, Western COS Cells Cell Line Chlorocebus aethiops Flow Cytometry Macrophages / cytology Macrophages / metabolism* Membrane Proteins / chemistry Membrane Proteins / genetics Membrane Proteins / metabolism Mice Mice, Knockout Mitogen-Activated Protein Kinases / metabolism NFATC Transcription Factors / genetics NFATC Transcription Factors / metabolism Osteoclasts / cytology Osteoclasts / metabolism RANK Ligand / genetics RANK Ligand / metabolism* Receptor Activator of Nuclear Factor-kappa B / chemistry Receptor Activator of Nuclear Factor-kappa B / genetics Receptor Activator of Nuclear Factor-kappa B / metabolism* Reverse Transcriptase Polymerase Chain Reaction Solubility TNF Receptor-Associated Factor 6 / genetics TNF Receptor-Associated Factor 6 / metabolism Transfection Up-Regulation |
| IF | 4.886 |
| 引用数 | 11 |
| 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 | 3 |
| 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 | RAW 264(RCB0535) COS-7(RCB0539) |