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
|
リソース情報 |
遺伝子材料 |
pCMV_S-FLAG (RDB05956) |