dc.contributor.author | Kirak, Oktay | |
dc.contributor.author | Efeyan, Alejo | |
dc.contributor.author | Schweitzer, Lawrence David | |
dc.contributor.author | Bilate, Angelina M | |
dc.contributor.author | Chang, Steven H. | |
dc.contributor.author | Lamming, Dudley | |
dc.contributor.author | Sabatini, David | |
dc.date.accessioned | 2017-04-12T19:34:05Z | |
dc.date.available | 2017-04-12T19:34:05Z | |
dc.date.issued | 2014-04 | |
dc.date.submitted | 2014-03 | |
dc.identifier.issn | 1534-5807 | |
dc.identifier.issn | 1878-1551 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/108081 | |
dc.description.abstract | The 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.sponsorship | United States. National Institutes of Health (R01 CA129105) | en_US |
dc.description.sponsorship | United States. National Institutes of Health (R01 CA103866) | en_US |
dc.description.sponsorship | United States. National Institutes of Health (R01 AI047389) | en_US |
dc.description.sponsorship | United States. National Institutes of Health (R21 AG042876) | en_US |
dc.description.sponsorship | American Federation for Aging Research | en_US |
dc.description.sponsorship | Starr Foundation | en_US |
dc.description.sponsorship | David H. Koch Institute for Integrative Cancer Research at MIT. Frontier Research Program | en_US |
dc.description.sponsorship | Ellison Medical Foundation | en_US |
dc.description.sponsorship | United States. National Institutes of Health (AG041765) | en_US |
dc.description.sponsorship | National Cancer Institute (U.S.) (F31CA167872) | en_US |
dc.language.iso | en_US | |
dc.publisher | Elsevier | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1016/j.devcel.2014.03.017 | en_US |
dc.rights | Creative Commons Attribution-NonCommercial-NoDerivs License | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en_US |
dc.source | PMC | en_US |
dc.title | RagA, but Not RagB, Is Essential for Embryonic Development and Adult Mice | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Efeyan, 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 Inc | en_US |
dc.contributor.department | Broad Institute of MIT and Harvard | en_US |
dc.contributor.mitauthor | Efeyan, Alejo | |
dc.contributor.mitauthor | Schweitzer, Lawrence David | |
dc.contributor.mitauthor | Bilate, Angelina M | |
dc.contributor.mitauthor | Chang, Steven H. | |
dc.contributor.mitauthor | Lamming, Dudley | |
dc.contributor.mitauthor | Sabatini, David | |
dc.relation.journal | Developmental Cell | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Efeyan, Alejo; Schweitzer, Lawrence D.; Bilate, Angelina M.; Chang, Steven; Kirak, Oktay; Lamming, Dudley W.; Sabatini, David M. | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-9765-4016 | |
dc.identifier.orcid | https://orcid.org/0000-0002-0079-4467 | |
dc.identifier.orcid | https://orcid.org/0000-0002-1446-7256 | |
mit.license | PUBLISHER_CC | en_US |
mit.metadata.status | Complete | |