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dc.contributor.authorKirak, Oktay
dc.contributor.authorEfeyan, Alejo
dc.contributor.authorSchweitzer, Lawrence David
dc.contributor.authorBilate, Angelina M
dc.contributor.authorChang, Steven H.
dc.contributor.authorLamming, Dudley
dc.contributor.authorSabatini, David
dc.date.accessioned2017-04-12T19:34:05Z
dc.date.available2017-04-12T19:34:05Z
dc.date.issued2014-04
dc.date.submitted2014-03
dc.identifier.issn1534-5807
dc.identifier.issn1878-1551
dc.identifier.urihttp://hdl.handle.net/1721.1/108081
dc.description.abstractThe mechanistic target of rapamycin complex 1 (mTORC1) integrates cues from growth factors and nutrients to control metabolism. In contrast to the growth factor input, genetic disruption of nutrient-dependent activation of mTORC1 in mammals remains unexplored. We engineered mice lacking RagA and RagB genes, which encode the GTPases responsible for mTORC1 activation by nutrients. RagB has limited expression, and its loss shows no effects on mammalian physiology. RagA deficiency leads to E10.5 embryonic death, loss of mTORC1 activity, and severe growth defects. Primary cells derived from these mice exhibit no regulation of mTORC1 by nutrients and maintain high sensitivity to growth factors. Deletion of RagA in adult mice is lethal. Upon RagA loss, a myeloid population expands in peripheral tissues. RagA-specific deletion in liver increases cellular responses to growth factors. These results show the essentiality of nutrient sensing for mTORC1 activity in mice and its suppression of PI3K/Akt signaling.en_US
dc.description.sponsorshipUnited States. National Institutes of Health (R01 CA129105)en_US
dc.description.sponsorshipUnited States. National Institutes of Health (R01 CA103866)en_US
dc.description.sponsorshipUnited States. National Institutes of Health (R01 AI047389)en_US
dc.description.sponsorshipUnited States. National Institutes of Health (R21 AG042876)en_US
dc.description.sponsorshipAmerican Federation for Aging Researchen_US
dc.description.sponsorshipStarr Foundationen_US
dc.description.sponsorshipDavid H. Koch Institute for Integrative Cancer Research at MIT. Frontier Research Programen_US
dc.description.sponsorshipEllison Medical Foundationen_US
dc.description.sponsorshipUnited States. National Institutes of Health (AG041765)en_US
dc.description.sponsorshipNational Cancer Institute (U.S.) (F31CA167872)en_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.devcel.2014.03.017en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourcePMCen_US
dc.titleRagA, but Not RagB, Is Essential for Embryonic Development and Adult Miceen_US
dc.typeArticleen_US
dc.identifier.citationEfeyan, Alejo; Schweitzer, Lawrence D.; Bilate, Angelina M.; Chang, Steven; Kirak, Oktay; Lamming, Dudley W. and Sabatini, David M. “RagA, but Not RagB, Is Essential for Embryonic Development and Adult Mice.” Developmental Cell 29, no. 3 (May 2014): 321–329. © 2014 Elsevier Incen_US
dc.contributor.departmentBroad Institute of MIT and Harvarden_US
dc.contributor.mitauthorEfeyan, Alejo
dc.contributor.mitauthorSchweitzer, Lawrence David
dc.contributor.mitauthorBilate, Angelina M
dc.contributor.mitauthorChang, Steven H.
dc.contributor.mitauthorLamming, Dudley
dc.contributor.mitauthorSabatini, David
dc.relation.journalDevelopmental Cellen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsEfeyan, Alejo; Schweitzer, Lawrence D.; Bilate, Angelina M.; Chang, Steven; Kirak, Oktay; Lamming, Dudley W.; Sabatini, David M.en_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0001-9765-4016
dc.identifier.orcidhttps://orcid.org/0000-0002-0079-4467
dc.identifier.orcidhttps://orcid.org/0000-0002-1446-7256
mit.licensePUBLISHER_CCen_US
mit.metadata.statusComplete


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