| RRC ID |
12035
|
| 著者 |
Yogo K, Mizutamari M, Mishima K, Takenouchi H, Ishida-Kitagawa N, Sasaki T, Takeya T.
|
| タイトル |
Src homology 2 (SH2)-containing 5'-inositol phosphatase localizes to podosomes, and the SH2 domain is implicated in the attenuation of bone resorption in osteoclasts.
|
| ジャーナル |
Endocrinology
|
| Abstract |
c-Src plays an important role in bone resorption by osteoclasts. Here, we show using wild-type and ship(-/-) osteoclasts that Src homology 2 (SH2)-containing 5'-inositol phosphatase (SHIP) appeared to negatively regulate bone resorption activated by c-Src. SHIP was found to localize to podosomes under the influence of c-Src, and the presence of either the amino-terminal region comprising the SH2 domain or the carboxyl-terminal region was sufficient for its localization. Although SHIP lacking a functional SH2 domain was still found in podosomes, it could not rescue the hyper-bone resorbing activity and hypersensitivity to receptor activator of nuclear factor-kappaB ligand in ship(-/-) osteoclasts, suggesting that the localization of SHIP to podosomes per se was not sufficient and the SH2 domain was indispensable for its function. Cas and c-Cbl, known to function in podosomes of osteoclasts, were identified as novel proteins binding to the SHIP SH2 domain by mass spectrometric analysis, and this interaction appeared to be dependent on the Src kinase activity. These results demonstrate that c-Src enhances the translocation of SHIP to podosomes and regulates its function there through the SH2 domain, leading to an attenuation of bone resorption.
|
| 巻・号 |
147(7)
|
| ページ |
3307-17
|
| 公開日 |
2006-7-1
|
| DOI |
10.1210/en.2005-1309
|
| PII |
en.2005-1309
|
| PMID |
16601135
|
| MeSH |
Animals
Bone Resorption*
Cell Line
Inositol Polyphosphate 5-Phosphatases
Mass Spectrometry
Mice
NF-kappa B / metabolism
NIH 3T3 Cells
Osteoclasts / enzymology
Osteoclasts / metabolism*
Phosphatidylinositols / metabolism
Phosphoric Monoester Hydrolases / metabolism*
Phosphoric Monoester Hydrolases / physiology*
Protein Binding
Protein Transport
Proto-Oncogene Proteins pp60(c-src) / chemistry*
src Homology Domains*
|
| IF |
3.934
|
| 引用数 |
20
|
|
WOS 分野
|
ENDOCRINOLOGY & METABOLISM
|
| リソース情報 |
| 遺伝子材料 |
pCAhMCSF Human M-CSF (RDB1524) |
