論文 - 詳細
| RRC ID | 58328 |
|---|---|
| 著者 | Hwang SH, Bang S, Kim W, Chung J. |
| タイトル | Von Hippel-Lindau tumor suppressor (VHL) stimulates TOR signaling by interacting with phosphoinositide 3-kinase (PI3K). |
| ジャーナル | J Biol Chem |
| Abstract |
Cell growth is positively controlled by the phosphoinositide 3-kinase (PI3K)-target of rapamycin (TOR) signaling pathway under conditions of abundant growth factors and nutrients. To discover additional mechanisms that regulate cell growth, here we performed RNAi-based mosaic analyses in the Drosophila fat body, the primary metabolic organ in the fly. Unexpectedly, the knockdown of the Drosophila von Hippel-Lindau (VHL) gene markedly decreased cell size and body size. These cell growth phenotypes induced by VHL loss of function were recovered by activation of TOR signaling in Drosophila Consistent with the genetic interactions between VHL and the signaling components of PI3K-TOR pathway in Drosophila, we observed that VHL loss of function in mammalian cells causes decreased phosphorylation of ribosomal protein S6 kinase and Akt, which represent the main activities of this pathway. We further demonstrate that VHL activates TOR signaling by directly interacting with the p110 catalytic subunit of PI3K. On the basis of the evolutionarily conserved regulation of PI3K-TOR signaling by VHL observed here, we propose that VHL plays an important role in the regulation and maintenance of proper cell growth in metazoans. |
| 巻・号 | 295(8) |
| ページ | 2336-2347 |
| 公開日 | 2020-2-21 |
| DOI | 10.1074/jbc.RA119.011596 |
| PII | S0021-9258(17)48270-6 |
| PMID | 31959630 |
| PMC | PMC7039557 |
| MeSH | Animals Body Size Carrier Proteins / metabolism* Cell Size Drosophila Proteins / metabolism* Drosophila melanogaster / cytology Drosophila melanogaster / metabolism* HEK293 Cells Humans Hypoxia-Inducible Factor 1, alpha Subunit / metabolism Mice Phosphatidylinositol 3-Kinase / metabolism* Protein Binding Receptor Protein-Tyrosine Kinases / metabolism* Signal Transduction* |
| IF | 4.238 |
| 引用数 | 0 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 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 | |
| ショウジョウバエ | 5671R-1 7590R-1 |