| RRC ID |
12044
|
| 著者 |
Koga S, Yogo K, Yoshikawa K, Samori H, Goto M, Uchida T, Ishida N, Takeya T.
|
| タイトル |
Physical and functional association of c-Src and adhesion and degranulation promoting adaptor protein (ADAP) in osteoclastogenesis in vitro.
|
| ジャーナル |
J Biol Chem
|
| Abstract |
c-Src plays a crucial role in osteoclastogenesis. In this study, we searched for c-Src-binding proteins using a combination of pull-down assays and mass spectrometric analysis, and identified the association of adhesion and degranulation promoting adaptor protein (ADAP) with c-Src in RAW264 cells and osteoclast precursors prepared from bone marrow cells. The kinase activity and the SH2 domain of c-Src were required for this association and Tyr807 in the extreme carboxyl terminus of ADAP was identified as a major recognition site. ADAP was found to be expressed in cells at the prefusion stage and localized mainly in the leading edge of lamellipodia and in pseudopodia. Tyrosine phosphorylation of ADAP was induced in an integrin-dependent manner, and the level was Src kinase-dependent. ADAP-knockdown RAW264 cells showed retarded migration and formed few multinucleated cells. Cas, known to be phosphorylated by c-Src, was identified as a major tyrosine-phosphorylated protein in differentiating RAW264 cells and the phosphorylation appeared to be decreased in ADAP-knockdown cells. ADAP thus may play an important role as a partner of c-Src for cell migration and progression to the multinucleated cell stage in osteoclastogenesis in vitro.
|
| 巻・号 |
280(36)
|
| ページ |
31564-71
|
| 公開日 |
2005-9-9
|
| DOI |
10.1074/jbc.M502703200
|
| PII |
S0021-9258(20)79270-7
|
| PMID |
16020549
|
| MeSH |
Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / physiology*
Animals
CSK Tyrosine-Protein Kinase
Cell Adhesion / physiology
Cell Degranulation / physiology*
Cell Differentiation / physiology*
Cell Line
Cell Movement / physiology
Crk-Associated Substrate Protein
Female
Gene Expression Profiling
Humans
Mice
NIH 3T3 Cells
Osteoclasts / cytology
Osteoclasts / physiology*
Phosphorylation
Protein-Tyrosine Kinases / physiology*
Proteins / metabolism
RNA, Small Interfering / metabolism
Retinoblastoma-Like Protein p130
Stem Cells / cytology
Stem Cells / physiology
Tyrosine / genetics
Tyrosine / metabolism
src-Family Kinases
|
| IF |
4.238
|
| 引用数 |
10
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| 遺伝子材料 |
pCAhMCSF Human M-CSF (RDB01524) |
