{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:15:03Z","timestamp":1790734503605,"version":"4.1.0"},"reference-count":57,"publisher":"American Society for Cell Biology (ASCB)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2010,3]]},"abstract":"<jats:p>The multisubunit mTORC1 complex integrates signals from growth factors and nutrients to regulate protein synthesis, cell growth, and autophagy. To examine how endocytic trafficking might be involved in nutrient regulation of mTORC1, we perturbed specific endocytic trafficking pathways and measured mTORC1 activity using S6K1 as a readout. When early\/late endosomal conversion was blocked by either overexpression of constitutively active Rab5 (Rab5CA) or knockdown of the Rab7 GEF hVps39, insulin- and amino acid\u2013stimulated mTORC1\/S6K1 activation were inhibited, and mTOR localized to hybrid early\/late endosomes. Inhibition of other stages of endocytic trafficking had no effect on mTORC1. Overexpression of Rheb, which activates mTOR independently of mTOR localization, rescued mTORC1 signaling in cells expressing Rab5CA, whereas hyperactivation of endogenous Rheb in TSC2\u2212\/\u2212 MEFs did not. These data suggest that integrity of late endosomes is essential for amino acid\u2013 and insulin-stimulated mTORC1 signaling and that blocking the early\/late endosomal conversion prevents mTOR from interacting with Rheb in the late endosomal compartment.<\/jats:p>","DOI":"10.1091\/mbc.e09-09-0756","type":"journal-article","created":{"date-parts":[[2010,1,7]],"date-time":"2010-01-07T03:19:34Z","timestamp":1262834374000},"page":"833-841","source":"Crossref","is-referenced-by-count":141,"title":["The Late Endosome is Essential for mTORC1 Signaling"],"prefix":"10.1091","volume":"21","author":[{"given":"Rory J.","family":"Flinn","sequence":"first","affiliation":[{"name":"*Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yan","sequence":"additional","affiliation":[{"name":"*Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumanta","family":"Goswami","sequence":"additional","affiliation":[{"name":"Department of Biology, Yeshiva University, New York, NY 10033; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Parker","sequence":"additional","affiliation":[{"name":"Protein Phosphorylation Laboratory, Cancer Research UK, London Research Institute, London WC2 3PX, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M.","family":"Backer","sequence":"additional","affiliation":[{"name":"*Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1076","reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"6361","DOI":"10.1038\/sj.onc.1209882","volume":"25","author":"Avruch J.","year":"2006","journal-title":"Oncogene"},{"key":"B2","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.molcel.2009.06.033","volume":"35","author":"Binda M.","year":"2009","journal-title":"Mol. 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