論文 - 詳細
| RRC ID | 47682 |
|---|---|
| 著者 | Tatebe H, Murayama S, Yonekura T, Hatano T, Richter D, Furuya T, Kataoka S, Furuita K, Kojima C, Shiozaki K. |
| タイトル | Substrate specificity of TOR complex 2 is determined by a ubiquitin-fold domain of the Sin1 subunit. |
| ジャーナル | Elife |
| Abstract |
The target of rapamycin (TOR) protein kinase forms multi-subunit TOR complex 1 (TORC1) and TOR complex 2 (TORC2), which exhibit distinct substrate specificities. Sin1 is one of the TORC2-specific subunit essential for phosphorylation and activation of certain AGC-family kinases. Here, we show that Sin1 is dispensable for the catalytic activity of TORC2, but its conserved region in the middle (Sin1CRIM) forms a discrete domain that specifically binds the TORC2 substrate kinases. Sin1CRIM fused to a different TORC2 subunit can recruit the TORC2 substrate Gad8 for phosphorylation even in the sin1 null mutant of fission yeast. The solution structure of Sin1CRIM shows a ubiquitin-like fold with a characteristic acidic loop, which is essential for interaction with the TORC2 substrates. The specific substrate-recognition function is conserved in human Sin1CRIM, which may represent a potential target for novel anticancer drugs that prevent activation of the mTORC2 substrates such as AKT. |
| 巻・号 | 6 |
| 公開日 | 2017-3-7 |
| DOI | 10.7554/eLife.19594 |
| PII | e19594 |
| PMID | 28264193 |
| PMC | PMC5340527 |
| MeSH | Adaptor Proteins, Signal Transducing / chemistry Adaptor Proteins, Signal Transducing / genetics Adaptor Proteins, Signal Transducing / metabolism Carrier Proteins / chemistry* Carrier Proteins / genetics Carrier Proteins / metabolism* Conserved Sequence HEK293 Cells Humans Magnetic Resonance Spectroscopy Mechanistic Target of Rapamycin Complex 2 / metabolism* Models, Molecular Protein Binding Protein Conformation Protein Folding Protein Interaction Mapping Schizosaccharomyces / enzymology Schizosaccharomyces pombe Proteins / chemistry* Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism* Substrate Specificity |
| IF | 7.08 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 6 |
| 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 | |
| 酵母 | FYC550(psk1)? |
| ヒト・動物細胞 | MCF7(RCB1904) 293T(RCB2202) |