NLK phosphorylates Raptor to mediate stress-induced mTORC1 inhibition
| العنوان: | NLK phosphorylates Raptor to mediate stress-induced mTORC1 inhibition |
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| المؤلفون: | Kun-Liang Guan, Jenna L. Jewell, Hai Xin Yuan, Ryan C. Russell, Zhen Wang, Fulong Li, Fa-Xing Yu |
| المصدر: | Genes & development, vol 29, iss 22 |
| بيانات النشر: | Cold Spring Harbor Laboratory, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | NLK, 1.1 Normal biological development and functioning, mTORC1, Mechanistic Target of Rapamycin Complex 1, Biology, Medical and Health Sciences, mTORC2, 03 medical and health sciences, 0302 clinical medicine, Underpinning research, Osmotic Pressure, Genetics, cancer, Humans, Gene Knock-In Techniques, Phosphorylation, Mechanistic target of rapamycin, PI3K/AKT/mTOR pathway, Adaptor Proteins, Signal Transducing, 030304 developmental biology, 0303 health sciences, Cell growth, Kinase, TOR Serine-Threonine Kinases, Psychology and Cognitive Sciences, HEK 293 cells, Signal Transducing, Adaptor Proteins, stress response, Regulatory-Associated Protein of mTOR, Biological Sciences, Raptor, Cell biology, Enzyme Activation, HEK293 Cells, Multiprotein Complexes, mTOR, biology.protein, Cancer research, Mitogen-Activated Protein Kinases, biological phenomena, cell phenomena, and immunity, Gene Deletion, 030217 neurology & neurosurgery, Research Paper, Developmental Biology |
| الوصف: | The mechanistic target of rapamycin (mTOR) is a central cell growth controller and forms two distinct complexes: mTORC1 and mTORC2. mTORC1 integrates a wide range of upstream signals, both positive and negative, to regulate cell growth. Although mTORC1 activation by positive signals, such as growth factors and nutrients, has been extensively investigated, the mechanism of mTORC1 regulation by stress signals is less understood. In this study, we identified the Nemo-like kinase (NLK) as an mTORC1 regulator in mediating the osmotic and oxidative stress signals. NLK inhibits mTORC1 lysosomal localization and thereby suppresses mTORC1 activation. Mechanistically, NLK phosphorylates Raptor on S863 to disrupt its interaction with the Rag GTPase, which is important for mTORC1 lysosomal recruitment. Cells with Nlk deletion or knock-in of the Raptor S863 phosphorylation mutants are defective in the rapid mTORC1 inhibition upon osmotic stress. Our study reveals a function of NLK in stress-induced mTORC1 modulation and the underlying biochemical mechanism of NLK in mTORC1 inhibition in stress response. |
| وصف الملف: | application/pdf |
| تدمد: | 1549-5477 0890-9369 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0f309a9310e80c56ac7c2ca7f3465548Test https://doi.org/10.1101/gad.265116.115Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0f309a9310e80c56ac7c2ca7f3465548 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15495477 08909369 |
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