論文 - 詳細
| RRC ID | 43169 |
|---|---|
| 著者 | Horiuchi K, Miyamoto T, Takaishi H, Hakozaki A, Kosaki N, Miyauchi Y, Furukawa M, Takito J, Kaneko H, Matsuzaki K, Morioka H, Blobel CP, Toyama Y. |
| タイトル | Cell surface colony-stimulating factor 1 can be cleaved by TNF-alpha converting enzyme or endocytosed in a clathrin-dependent manner. |
| ジャーナル | J Immunol |
| Abstract |
CSF-1 is a hemopoietic growth factor, which plays an essential role in macrophage and osteoclast development. Alternative splice variants of CSF-1 are synthesized as soluble or membrane-anchored molecules, although membrane CSF-1 (mCSF-1) can be cleaved from the cell membrane to become soluble CSF-1. The activities involved in this proteolytic processing, also referred to as ectodomain shedding, remain poorly characterized. In the present study, we examined the properties of the mCSF-1 sheddase in cell-based assays. Shedding of mCSF-1 was up-regulated by phorbol ester treatment and was inhibited by the metalloprotease inhibitors GM6001 and tissue inhibitor of metalloproteases 3. Moreover, the stimulated shedding of mCSF-1 was abrogated in fibroblasts lacking the TNF-alpha converting enzyme (TACE, also known as a disintegrin and metalloprotease 17) and was rescued by expression of wild-type TACE in these cells, strongly suggesting that the stimulated shedding is TACE dependent. Additionally, we observed that mCSF-1 is predominantly localized to intracellular membrane compartments and is efficiently internalized in a clathrin-dependent manner. These results indicate that the local availability of mCSF-1 is actively regulated by ectodomain shedding and endocytosis. This mechanism may have important implications for the development and survival of monocyte lineage cells. |
| 巻・号 | 179(10) |
| ページ | 6715-24 |
| 公開日 | 2007-11-15 |
| DOI | 10.4049/jimmunol.179.10.6715 |
| PII | 179/10/6715 |
| PMID | 17982061 |
| MeSH | ADAM Proteins / antagonists & inhibitors ADAM Proteins / metabolism* ADAM17 Protein Alternative Splicing / drug effects Alternative Splicing / physiology Animals COS Cells Carcinogens / pharmacology Cell Survival / drug effects Cell Survival / physiology Chlorocebus aethiops Clathrin / metabolism* Dipeptides / pharmacology Endocytosis / physiology* Macrophage Colony-Stimulating Factor / metabolism* Macrophages / metabolism* Membrane Proteins / metabolism Mice Osteoclasts / metabolism* Phorbol Esters / pharmacology Protease Inhibitors / pharmacology Protein Structure, Tertiary / physiology Tissue Inhibitor of Metalloproteinase-3 / metabolism |
| IF | 4.886 |
| 引用数 | 34 |
| 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 | ST2(RCB0224) COS-7(RCB0539) |