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dc.contributor.authorLong, Xiaomeng
dc.contributor.authorOrtiz-Vega, Sara
dc.contributor.authorLin, Yenshou
dc.contributor.authorAvruch, Joseph
dc.date.accessioned2019-10-05T03:29:32Z
dc.date.issued2005
dc.identifier.citationLong, Xiaomeng, Sara Ortiz-Vega, Yenshou Lin, and Joseph Avruch. 2005. “Rheb Binding to Mammalian Target of Rapamycin (mTOR) Is Regulated by Amino Acid Sufficiency.” Journal of Biological Chemistry 280 (25): 23433–36. https://doi.org/10.1074/jbc.c500169200.
dc.identifier.issn0021-9258
dc.identifier.issn1083-351X
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41483067*
dc.description.abstractThe removal of extracellular amino acids or leucine alone inhibits the ability of the mammalian target of rapamycin ( mTOR) to signal to the raptor-dependent substrates, p70 S6 kinase and 4E-BP. This inhibition can be overcome by overexpression of the Rheb GTPase. Rheb binds directly to the amino-terminal lobe of the mTOR catalytic domain, and activates mTOR kinase in a GTP-dependent manner. Herein we show that the binding of Rheb to endogenous and recombinant mTOR is reversibly inhibited by withdrawal of all extracellular amino acids or just leucine. The effect of amino acid withdrawal is not attributable to changes in Rheb-GTP charging; amino acid withdrawal does not alter the GTP charging of recombinant Rheb. Moreover, the binding of mTOR to Rheb mutants that are unable to bind guanyl nucleotide in vivo is also inhibited by amino withdrawal. The inhibitory effect of amino acid withdrawal is exerted through an action on mTOR, at a site largely distinct from that responsible for the binding of Rheb; deletion of the larger, carboxyl-terminal lobe of the mTOR catalytic domain eliminates the inhibitory effect of amino acid withdrawal on Rheb binding, without altering Rheb binding per se. The lesser ability of the mTOR catalytic domain to bind Rheb after amino acid withdrawal does not persist after extraction and purification of the mTOR polypeptide. Amino acid withdrawl may generate an inhibitor of the Rheb-mTOR interaction that interferes with the signaling function of TOR complex 1.
dc.language.isoen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology
dash.licenseLAA
dc.titleRheb Binding to Mammalian Target of Rapamycin (mTOR) Is Regulated by Amino Acid Sufficiency
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalThe Journal of Biological Chemistry
dash.depositing.authorAvruch, Joseph::9aac9685759478ee19677d9b77258031::600
dc.date.available2019-10-05T03:29:32Z
dash.workflow.comments1Science Serial ID 106338
dc.identifier.doi10.1074/jbc.C500169200
dash.source.volume280;25
dash.source.page23433-23436


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