Role of FLCN Phosphorylation in Insulin‐Mediated mTORC1 Activation and Tumorigenesis
Abstract: The amino acid‐stimulated Rag GTPase pathway is one of the main pathways that regulate mechanistic target of rapamycin complex 1 (mTORC1) activation and function, but little is known about the effects of growth factors on Rag GTPase‐mediated mTORC1 activation. Here, a highly conserved insulin‐responsive phosphorylation site on folliculin (FLCN), Ser62, that is phosphorylates by AKT1 is identified and characterized. mTORC2‐AKT1 is localized on lysosomes, and RagD‐specific recruitment of mTORC2‐AKT1 on lysosomes is identified as an essential step in insulin‐AKT1‐mediated FLCN phosphorylation. Additionally, FLCN phosphorylation inhibits the activity of RagC GTPase and is essential for insulin‐induced mTORC1 activation. Functionally, phosphorylated FLCN promotes cell viability and induces autophagy, and also regulates in vivo tumor growth in an mTORC1‐dependent manner. Its expression is also positively correlated with mTORC1 activity in colon cancer, clear cell renal cell carcinoma, and chordoma. These results indicate that FLCN is an important intermediate for cross‐talk between the amino acid and growth factor pathways. Further, FLCN phosphorylation may be a promising therapeutic target for diseases characterized by mTORC1 dysregulation.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Role of FLCN Phosphorylation in Insulin‐Mediated mTORC1 Activation and Tumorigenesis ; day:21 ; month:04 ; year:2023 ; extent:14
Advanced science ; (21.04.2023) (gesamt 14)
- Creator
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Wang, Guoyan
Chen, Lei
Lei, Xinjian
Qin, Senlin
Geng, Huijun
Zheng, Yining
Xia, Chao
Yao, Junhu
Meng, Tong
Deng, Lu
- DOI
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10.1002/advs.202206826
- URN
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urn:nbn:de:101:1-2023042415512236876974
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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14.08.2025, 10:58 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Wang, Guoyan
- Chen, Lei
- Lei, Xinjian
- Qin, Senlin
- Geng, Huijun
- Zheng, Yining
- Xia, Chao
- Yao, Junhu
- Meng, Tong
- Deng, Lu
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