論文 - 詳細
| RRC ID | 49278 |
|---|---|
| 著者 | Kuki K, Yamaguchi N, Iwasawa S, Takakura Y, Aoyama K, Yuki R, Nakayama Y, Kuga T, Hashimoto Y, Tomonaga T, Yamaguchi N. |
| タイトル | Enhancement of TGF-β-induced Smad3 activity by c-Abl-mediated tyrosine phosphorylation of its coactivator SKI-interacting protein (SKIP). |
| ジャーナル | Biochem Biophys Res Commun |
| Abstract |
c-Abl is a non-receptor-type tyrosine kinase that plays an important role in cell proliferation, migration, apoptosis, and fibrosis. Furthermore, although c-Abl is involved in transforming growth factor-β (TGF-β) signaling, its molecular functions in TGF-β signaling are not fully understood. Here, we found that c-Abl phosphorylates SKI-interacting protein (SKIP), a nuclear cofactor of the transcription factor Smad3. The c-Abl inhibitor imatinib suppressed TGF-β-induced expression of Smad3 targets as well as SKIP/Smad3 interaction. TGF-β-stimulation induced tyrosine phosphorylation of SKIP, and this phosphorylation was suppressed by imatinib. Tyr292, Tyr430, and Tyr433 residues in SKIP were shown to be involved in c-Abl-mediated phosphorylation. Phosphomimetic glutamic acid substitution at Tyr292 in SKIP enhanced, whereas its phospho-dead phenylalanine substitution attenuated TGF-β-induced SKIP/Smad3 interaction. Moreover, the phosphomimetic mutant of SKIP augmented transcriptional activity of Smad3. Taken together, these results suggest that c-Abl phosphorylates SKIP mainly at Tyr292 and promotes SKIP/Smad3 interaction for the full activation of TGF-β/Smad3 signaling. |
| 巻・号 | 490(3) |
| ページ | 1045-1051 |
| 公開日 | 2017-8-26 |
| DOI | 10.1016/j.bbrc.2017.06.163 |
| PII | S0006-291X(17)31294-9 |
| PMID | 28666867 |
| MeSH | A549 Cells Animals COS Cells Chlorocebus aethiops HeLa Cells Humans Nuclear Receptor Coactivators / metabolism* Phosphorylation Protein Interaction Maps Proto-Oncogene Proteins c-abl / metabolism* Smad3 Protein / metabolism* Transforming Growth Factor beta / metabolism* Tyrosine / metabolism* |
| IF | 2.985 |
| 引用数 | 4 |
| 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 | |
| 遺伝子材料 | pCMV_S-FLAG (RDB05956) |