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)