| 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
|
| リソース情報 |
| ヒト・動物細胞 |
ST2(RCB0224)
COS-7(RCB0539) |
