FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1976643149> ?p ?o ?g. }

• W1976643149 endingPage "7879" @default.
• W1976643149 startingPage "7866" @default.
• W1976643149 abstract "The mammalian target of rapamycin (mTOR) Ser/Thr kinase signals in at least two multiprotein complexes distinguished by their different partners and sensitivities to rapamycin. Acute rapamycin inhibits signaling by mTOR complex 1 (mTORC1) but not mTOR complex 2 (mTORC2), which both promote cell growth, proliferation, and survival. Although mTORC2 regulation remains poorly defined, diverse cellular mitogens activate mTORC1 signaling in a manner that requires sufficient levels of amino acids and cellular energy. Before the identification of distinct mTOR complexes, mTOR was reported to autophosphorylate on Ser-2481 in vivo in a rapamycin- and amino acid-insensitive manner. These results suggested that modulation of mTOR intrinsic catalytic activity does not universally underlie mTOR regulation. Here we re-examine the regulation of mTOR Ser-2481 autophosphorylation (Ser(P)-2481) in vivo by studying mTORC-specific Ser(P)-2481 in mTORC1 and mTORC2, with a primary focus on mTORC1. In contrast to previous work, we find that acute rapamycin and amino acid withdrawal markedly attenuate mTORC1-associated mTOR Ser(P)-2481 in cycling cells. Although insulin stimulates both mTORC1- and mTORC2-associated mTOR Ser(P)-2481 in a phosphatidylinositol 3-kinase-dependent manner, rapamycin acutely inhibits insulin-stimulated mTOR Ser(P)-2481 in mTORC1 but not mTORC2. By interrogating diverse mTORC1 regulatory input, we find that without exception mTORC1-activating signals promote, whereas mTORC1-inhibitory signals decrease mTORC1-associated mTOR Ser(P)-2481. These data suggest that mTORC1- and likely mTORC2-associated mTOR Ser-2481 autophosphorylation directly monitors intrinsic mTORC-specific catalytic activity and reveal that rapamycin inhibits mTORC1 signaling in vivo by reducing mTORC1 catalytic activity. The mammalian target of rapamycin (mTOR) Ser/Thr kinase signals in at least two multiprotein complexes distinguished by their different partners and sensitivities to rapamycin. Acute rapamycin inhibits signaling by mTOR complex 1 (mTORC1) but not mTOR complex 2 (mTORC2), which both promote cell growth, proliferation, and survival. Although mTORC2 regulation remains poorly defined, diverse cellular mitogens activate mTORC1 signaling in a manner that requires sufficient levels of amino acids and cellular energy. Before the identification of distinct mTOR complexes, mTOR was reported to autophosphorylate on Ser-2481 in vivo in a rapamycin- and amino acid-insensitive manner. These results suggested that modulation of mTOR intrinsic catalytic activity does not universally underlie mTOR regulation. Here we re-examine the regulation of mTOR Ser-2481 autophosphorylation (Ser(P)-2481) in vivo by studying mTORC-specific Ser(P)-2481 in mTORC1 and mTORC2, with a primary focus on mTORC1. In contrast to previous work, we find that acute rapamycin and amino acid withdrawal markedly attenuate mTORC1-associated mTOR Ser(P)-2481 in cycling cells. Although insulin stimulates both mTORC1- and mTORC2-associated mTOR Ser(P)-2481 in a phosphatidylinositol 3-kinase-dependent manner, rapamycin acutely inhibits insulin-stimulated mTOR Ser(P)-2481 in mTORC1 but not mTORC2. By interrogating diverse mTORC1 regulatory input, we find that without exception mTORC1-activating signals promote, whereas mTORC1-inhibitory signals decrease mTORC1-associated mTOR Ser(P)-2481. These data suggest that mTORC1- and likely mTORC2-associated mTOR Ser-2481 autophosphorylation directly monitors intrinsic mTORC-specific catalytic activity and reveal that rapamycin inhibits mTORC1 signaling in vivo by reducing mTORC1 catalytic activity." @default.
• W1976643149 created "2016-06-24" @default.
• W1976643149 creator A5001189210 @default.
• W1976643149 creator A5004385645 @default.
• W1976643149 creator A5017680982 @default.
• W1976643149 creator A5019623840 @default.
• W1976643149 creator A5023733296 @default.
• W1976643149 creator A5043896468 @default.
• W1976643149 creator A5074288523 @default.
• W1976643149 date "2010-03-01" @default.
• W1976643149 modified "2023-10-16" @default.
• W1976643149 title "mTOR Ser-2481 Autophosphorylation Monitors mTORC-specific Catalytic Activity and Clarifies Rapamycin Mechanism of Action" @default.
• W1976643149 cites W1556721384 @default.
• W1976643149 cites W1573949141 @default.
• W1976643149 cites W1668086213 @default.
• W1976643149 cites W1797700808 @default.
• W1976643149 cites W1969319225 @default.
• W1976643149 cites W1976206793 @default.
• W1976643149 cites W1978240770 @default.
• W1976643149 cites W1983698019 @default.
• W1976643149 cites W1984736455 @default.
• W1976643149 cites W1987005832 @default.
• W1976643149 cites W1992170852 @default.
• W1976643149 cites W1992480202 @default.
• W1976643149 cites W1993431258 @default.
• W1976643149 cites W1994206543 @default.
• W1976643149 cites W1997053429 @default.
• W1976643149 cites W1998641189 @default.
• W1976643149 cites W1998762942 @default.
• W1976643149 cites W1999056466 @default.
• W1976643149 cites W2001259221 @default.
• W1976643149 cites W2001568034 @default.
• W1976643149 cites W2002031023 @default.
• W1976643149 cites W2002226709 @default.
• W1976643149 cites W2004582874 @default.
• W1976643149 cites W2006559495 @default.
• W1976643149 cites W2007110714 @default.
• W1976643149 cites W2008825756 @default.
• W1976643149 cites W2011282245 @default.
• W1976643149 cites W2011437516 @default.
• W1976643149 cites W2012142261 @default.
• W1976643149 cites W2015174638 @default.
• W1976643149 cites W2023012828 @default.
• W1976643149 cites W2025176940 @default.
• W1976643149 cites W2035521247 @default.
• W1976643149 cites W2041811289 @default.
• W1976643149 cites W2044301435 @default.
• W1976643149 cites W2048498664 @default.
• W1976643149 cites W2055729918 @default.
• W1976643149 cites W2056570604 @default.
• W1976643149 cites W2065887259 @default.
• W1976643149 cites W2066659565 @default.
• W1976643149 cites W2071618706 @default.
• W1976643149 cites W2081920342 @default.
• W1976643149 cites W2082853003 @default.
• W1976643149 cites W2087390102 @default.
• W1976643149 cites W2087812126 @default.
• W1976643149 cites W2089632625 @default.
• W1976643149 cites W2094941511 @default.
• W1976643149 cites W2097000222 @default.
• W1976643149 cites W2098912234 @default.
• W1976643149 cites W2099031084 @default.
• W1976643149 cites W2099544753 @default.
• W1976643149 cites W2101083009 @default.
• W1976643149 cites W2103470698 @default.
• W1976643149 cites W2109263914 @default.
• W1976643149 cites W2110443482 @default.
• W1976643149 cites W2124013343 @default.
• W1976643149 cites W2129307474 @default.
• W1976643149 cites W2134138119 @default.
• W1976643149 cites W2134757689 @default.
• W1976643149 cites W2136676465 @default.
• W1976643149 cites W2139856846 @default.
• W1976643149 cites W2144059623 @default.
• W1976643149 cites W2152289580 @default.
• W1976643149 cites W2152600551 @default.
• W1976643149 cites W2154106855 @default.
• W1976643149 cites W2159312214 @default.
• W1976643149 cites W2159714906 @default.
• W1976643149 cites W2163583831 @default.
• W1976643149 cites W4238567307 @default.
• W1976643149 doi "https://doi.org/10.1074/jbc.m109.096222" @default.
• W1976643149 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2832937" @default.
• W1976643149 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20022946" @default.
• W1976643149 hasPublicationYear "2010" @default.
• W1976643149 type Work @default.
• W1976643149 sameAs 1976643149 @default.
• W1976643149 citedByCount "205" @default.
• W1976643149 countsByYear W19766431492012 @default.
• W1976643149 countsByYear W19766431492013 @default.
• W1976643149 countsByYear W19766431492014 @default.
• W1976643149 countsByYear W19766431492015 @default.
• W1976643149 countsByYear W19766431492016 @default.
• W1976643149 countsByYear W19766431492017 @default.
• W1976643149 countsByYear W19766431492018 @default.
• W1976643149 countsByYear W19766431492019 @default.
• W1976643149 countsByYear W19766431492020 @default.
• W1976643149 countsByYear W19766431492021 @default.

• next