論文 - 詳細
| RRC ID | 28590 |
|---|---|
| 著者 | Watanabe Y, Itoh S, Goto T, Ohnishi E, Inamitsu M, Itoh F, Satoh K, Wiercinska E, Yang W, Shi L, Tanaka A, Nakano N, Mommaas AM, Shibuya H, Ten Dijke P, Kato M. |
| タイトル | TMEPAI, a transmembrane TGF-beta-inducible protein, sequesters Smad proteins from active participation in TGF-beta signaling. |
| ジャーナル | Mol Cell |
| Abstract |
Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine of key importance for controlling embryogenesis and tissue homeostasis. How TGF-beta signals are attenuated and terminated is not well understood. Here, we show that TMEPAI, a direct target gene of TGF-beta signaling, antagonizes TGF-beta signaling by interfering with TGF-beta type I receptor (TbetaRI)-induced R-Smad phosphorylation. TMEPAI can directly interact with R-Smads via a Smad interaction motif. TMEPAI competes with Smad anchor for receptor activation for R-Smad binding, thereby sequestering R-Smads from TbetaRI kinase activation. In mammalian cells, ectopic expression of TMEPAI inhibited TGF-beta-dependent regulation of plasminogen activator inhibitor-1, JunB, cyclin-dependent kinase inhibitors, and c-myc expression, whereas specific knockdown of TMEPAI expression prolonged duration of TGF-beta-induced Smad2 and Smad3 phosphorylation and concomitantly potentiated cellular responsiveness to TGF-beta. Consistently, TMEPAI inhibits activin-mediated mesoderm formation in Xenopus embryos. Therefore, TMEPAI participates in a negative feedback loop to control the duration and intensity of TGF-beta/Smad signaling. |
| 巻・号 | 37(1) |
| ページ | 123-34 |
| 公開日 | 2010-1-15 |
| DOI | 10.1016/j.molcel.2009.10.028 |
| PII | S1097-2765(09)00965-4 |
| PMID | 20129061 |
| MeSH | Activins / metabolism Animals COS Cells Cell Line Chlorocebus aethiops Embryo, Nonmammalian / metabolism Embryonic Development Humans Membrane Proteins / chemistry Membrane Proteins / genetics Membrane Proteins / physiology* Mesoderm / growth & development Mice Models, Biological NIH 3T3 Cells RNA, Messenger / metabolism Signal Transduction* Smad Proteins / metabolism* Transforming Growth Factor beta / metabolism* Xenopus |
| IF | 15.584 |
| 引用数 | 98 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| 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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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pCMVmmTMEPAI (RDB08015) pCMVhsTMEPAIa (RDB08016) pCMVhsTMEPAIb (RDB08017) pCMVhsTMEPAIc (RDB08018) |