論文 - 詳細
| RRC ID | 18927 |
|---|---|
| 著者 | Matsubara T, Ikeda F, Hata K, Nakanishi M, Okada M, Yasuda H, Nishimura R, Yoneda T. |
| タイトル | Cbp recruitment of Csk into lipid rafts is critical to c-Src kinase activity and bone resorption in osteoclasts. |
| ジャーナル | J Bone Miner Res |
| Abstract |
A tyrosine kinase, c-Src, that plays an indispensable role in ruffled border formation and bone resorption is constitutively active in osteoclasts. However, to date, the molecular mechanism underlying increased c-Src activity in osteoclasts is unknown. To address this, we first examined the expression levels and subcellular localization of Csk, a negative regulatory kinase for c-Src. We found that the expression level of Csk in osteoclasts was comparable with that of other tissues. However, in osteoclasts, Csk was hardly localized in lipid rafts, where c-Src is highly expressed. Interestingly, expression of Cbp, which recruits Csk into lipid rafts through physical interaction with Csk, was very low in osteoclasts compared with other tissues. To understand the importance of Cbp in osteoclasts, we introduced Cbp into osteoclasts using an adenovirus gene delivery system. Introduction of Cbp stimulated recruitment of Csk into lipid rafts and suppressed c-Src activity in a dose-dependent manner. Furthermore, introduction of Cbp markedly inhibited formation of actin rings and bone-resorbing activity in osteoclasts. In addition, treatment with RANKL and overexpression of TRAF6 or NFAT2 inhibited Cbp expression in the osteoclastogenic cell line RAW264.7 along with osteoclastic differentiation. NFAT2 overexpression also inhibited Cbp expression in spleen macrophages. Collectively, our results indicate that reduction in Cbp expression is responsible for maintaining high c-Src activity in osteoclasts. These findings contribute to an understanding of the unique regulatory system for c-Src in osteoclasts. |
| 巻・号 | 25(5) |
| ページ | 1068-76 |
| 公開日 | 2010-5-1 |
| DOI | 10.1359/jbmr.091039 |
| PMID | 19874196 |
| MeSH | Actins / metabolism Animals Apoptosis / drug effects Bone Resorption / genetics* CSK Tyrosine-Protein Kinase Cell Differentiation / physiology Cell Line Hydrazines Macrophages / physiology Membrane Microdomains / metabolism* Membrane Proteins / physiology* Mice Osteoclasts / metabolism* Phosphoproteins / physiology* Protein-Tyrosine Kinases / physiology* Pyrazines Quinolines Signal Transduction / physiology src-Family Kinases |
| IF | 5.854 |
| 引用数 | 10 |
| WOS 分野 | ENDOCRINOLOGY & METABOLISM |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 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 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |