Glutamine and asparagine activate mTORC1 independently of Rag GTPases
| Autor: | Jenna L. Jewell, Delong Meng, Qianmei Yang, Rishika Navlani, Anderson R. Frank, Chase H. Melick, Huanyu Wang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Arginine Glutamine Cell Cycle Proteins mTORC1 GTPase Nutrient sensing Mechanistic Target of Rapamycin Complex 1 Biochemistry Cell Line Mice 03 medical and health sciences Lysosome medicine Animals Humans Editors' Picks Asparagine Amino Acids Phosphorylation Molecular Biology Adaptor Proteins Signal Transducing Monomeric GTP-Binding Proteins Sirolimus chemistry.chemical_classification 030102 biochemistry & molecular biology Ribosomal Protein S6 Kinases 70-kDa Cell Biology Culture Media Amino acid Cell biology HEK293 Cells 030104 developmental biology medicine.anatomical_structure chemistry ADP-Ribosylation Factor 1 biological phenomena cell phenomena and immunity Lysosomes Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 295:2890-2899 |
| ISSN: | 0021-9258 |
| Popis: | Nutrient sensing by cells is crucial, and when this sensing mechanism is disturbed, human disease can occur. mTOR complex 1 (mTORC1) senses amino acids to control cell growth, metabolism, and autophagy. Leucine, arginine, and methionine signal to mTORC1 through the well-characterized Rag GTPase signaling pathway. In contrast, glutamine activates mTORC1 through a Rag GTPase-independent mechanism that requires ADP-ribosylation factor 1 (Arf1). Here, using several biochemical and genetic approaches, we show that eight amino acids filter through the Rag GTPase pathway. Like glutamine, asparagine signals to mTORC1 through Arf1 in the absence of the Rag GTPases. Both the Rag-dependent and Rag-independent pathways required the lysosome and lysosomal function for mTORC1 activation. Our results show that mTORC1 is differentially regulated by amino acids through two distinct pathways. |
| Databáze: | OpenAIRE |
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