dc.contributor.author | Cervantes, Christopher L. | |
dc.contributor.author | Lim, Daniel Cham-Chin | |
dc.contributor.author | Kang, Seong A. | |
dc.contributor.author | Pacold, Michael E. | |
dc.contributor.author | Lou, Hua Jane | |
dc.contributor.author | Ottina, Kathleen | |
dc.contributor.author | Gray, Nathanael S. | |
dc.contributor.author | Turk, Benjamin E. | |
dc.contributor.author | Yaffe, Michael B | |
dc.contributor.author | Sabatini, David | |
dc.date.accessioned | 2014-03-14T16:47:11Z | |
dc.date.available | 2014-03-14T16:47:11Z | |
dc.date.issued | 2013-07 | |
dc.date.submitted | 2013-02 | |
dc.identifier.issn | 0036-8075 | |
dc.identifier.issn | 1095-9203 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/85630 | |
dc.description.abstract | The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) protein kinase promotes growth and is the target of rapamycin, a clinically useful drug that also prolongs life span in model organisms. A persistent mystery is why the phosphorylation of many bona fide mTORC1 substrates is resistant to rapamycin. We find that the in vitro kinase activity of mTORC1 toward peptides encompassing established phosphorylation sites varies widely and correlates strongly with the resistance of the sites to rapamycin, as well as to nutrient and growth factor starvation within cells. Slight modifications of the sites were sufficient to alter mTORC1 activity toward them in vitro and to cause concomitant changes within cells in their sensitivity to rapamycin and starvation. Thus, the intrinsic capacity of a phosphorylation site to serve as an mTORC1 substrate, a property we call substrate quality, is a major determinant of its sensitivity to modulators of the pathway. Our results reveal a mechanism through which mTORC1 effectors can respond differentially to the same signals. | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Grant CA103866) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Grant AI047389) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Grant ES015339) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Grant GM59281) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Grant CA112967) | en_US |
dc.description.sponsorship | United States. Dept. of Defense (Grant W81XWH-07-0448) | en_US |
dc.description.sponsorship | W. M. Keck Foundation | en_US |
dc.description.sponsorship | LAM Foundation | en_US |
dc.language.iso | en_US | |
dc.publisher | American Association for the Advancement of Science (AAAS) | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1126/science.1236566 | en_US |
dc.rights | Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. | en_US |
dc.source | PMC | en_US |
dc.title | mTORC1 Phosphorylation Sites Encode Their Sensitivity to Starvation and Rapamycin | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Kang, S. A., M. E. Pacold, C. L. Cervantes, D. Lim, H. J. Lou, K. Ottina, N. S. Gray, B. E. Turk, M. B. Yaffe, and D. M. Sabatini. “mTORC1 Phosphorylation Sites Encode Their Sensitivity to Starvation and Rapamycin.” Science 341, no. 6144 (July 25, 2013): 1236566-1236566. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Whitehead Institute for Biomedical Research | en_US |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | en_US |
dc.contributor.mitauthor | Cervantes, Christopher L. | en_US |
dc.contributor.mitauthor | Lim, Daniel Cham-Chin | en_US |
dc.contributor.mitauthor | Yaffe, Michael B. | en_US |
dc.contributor.mitauthor | Sabatini, David M. | en_US |
dc.relation.journal | Science | 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 | Kang, S. A.; Pacold, M. E.; Cervantes, C. L.; Lim, D.; Lou, H. J.; Ottina, K.; Gray, N. S.; Turk, B. E.; Yaffe, M. B.; Sabatini, D. M. | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-9547-3251 | |
dc.identifier.orcid | https://orcid.org/0000-0002-1446-7256 | |
mit.license | PUBLISHER_POLICY | en_US |
mit.metadata.status | Complete | |