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Src regulates amino acid-mediated mTORC1 activation by disrupting GATOR1-Rag GTPase interaction
- Source :
- Nature Communications, Nature Communications, Vol 9, Iss 1, Pp 1-14 (2018)
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- The mechanistic target of rapamycin complex 1 (mTORC1) regulates cell survival and autophagy, and its activity is regulated by amino acid availability. Rag GTPase-GATOR1 interactions inhibit mTORC1 in the absence of amino acids, and GATOR1 release and activation of RagA/B promotes mTORC1 activity in the presence of amino acids. However, the factors that play a role in Rag-GATOR1 interaction are still poorly characterized. Here, we show that the tyrosine kinase Src is crucial for amino acid-mediated activation of mTORC1. Src acts upstream of the Rag GTPases by promoting dissociation of GATOR1 from the Rags, thereby determining mTORC1 recruitment and activation at the lysosomal surface. Accordingly, amino acid-mediated regulation of Src/mTORC1 modulates autophagy and cell size expansion. Finally, Src hyperactivation overrides amino acid signaling in the activation of mTORC1. These results shed light on the mechanisms underlying pathway dysregulation in many cancer types.<br />The growth-promoting activity of mTORC1 is regulated by amino acid availability via the Rag GTPases. Here, the authors demonstrate Src-dependent control of cell size and autophagy through disruption of the Rag GTPaseāGATOR1 complex and mTORC1 activation at the lysosomal surface.
- Subjects :
- 0301 basic medicine
Science
General Physics and Astronomy
mTORC1
GTPase
Mechanistic Target of Rapamycin Complex 1
Article
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Autophagy
lcsh:Science
chemistry.chemical_classification
Multidisciplinary
Cell Cycle
General Chemistry
Cell cycle
Cell biology
Amino acid
src-Family Kinases
030104 developmental biology
chemistry
lcsh:Q
biological phenomena, cell phenomena, and immunity
Signal transduction
Tyrosine kinase
Signal Transduction
Proto-oncogene tyrosine-protein kinase Src
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....1c033a14458d3498ac79a42451924644