| RRC ID |
18207
|
| 著者 |
Takahashi Y, Shimokawa N, Esmaeili-Mahani S, Morita A, Masuda H, Iwasaki T, Tamura J, Haglund K, Koibuchi N.
|
| タイトル |
Ligand-induced downregulation of TrkA is partly regulated through ubiquitination by Cbl.
|
| ジャーナル |
FEBS Lett
|
| Abstract |
Nerve growth factor (NGF) binding to its receptor TrkA, which belongs to the family of receptor tyrosine kinases (RTKs), is known to induce its internalization, endosomal trafficking and subsequent lysosomal degradation. The Cbl family of ubiquitin ligases plays a major role in mediating ubiquitination and degradation of RTKs. However, it is not known whether Cbl participates in mediating ubiquitination of TrkA. Here we report that c-Cbl mediates ligand-induced ubiquitination and degradation of TrkA. TrkA ubiquitination and degradation required direct interactions between c-Cbl and phosphorylated TrkA. c-Cbl and ubiquitinated TrkA are found in a complex after NGF stimulation and are degraded in lysosomes. Taken together, our data demonstrate that c-Cbl can induce downregulation of NGF-TrkA complexes through ubiquitination and degradation of TrkA.
|
| 巻・号 |
585(12)
|
| ページ |
1741-7
|
| 公開日 |
2011-6-23
|
| DOI |
10.1016/j.febslet.2011.04.056
|
| PII |
S0014-5793(11)00315-2
|
| PMID |
21570973
|
| MeSH |
Animals
Cell Line
Down-Regulation / drug effects*
Humans
Ligands
Lysosomes / metabolism
Mice
Nerve Growth Factor / metabolism
Phosphorylation
Proto-Oncogene Proteins c-cbl / metabolism*
Rats
Receptor, trkA / metabolism*
Ubiquitination / physiology*
|
| IF |
3.057
|
| 引用数 |
24
|
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
293(RCB1637)
PC-12(RCB0009) |
