Sestrin2 is a leucine sensor for the mTORC1 pathway
Leucine is a proteogenic amino acid that also regulates many aspects of mammalian physiology, in large part by activating the mTOR complex 1 (mTORC1) protein kinase, a master growth controller. Amino acids signal to mTORC1 through the Rag guanosine triphosphatases (GTPases). Several factors regulate...
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| Format: | Article |
| Language: | en_US |
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American Association for the Advancement of Science (AAAS)
2017
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| Online Access: | http://hdl.handle.net/1721.1/107960 https://orcid.org/0000-0002-9535-7664 https://orcid.org/0000-0001-9388-1633 https://orcid.org/0000-0002-9376-3984 https://orcid.org/0000-0002-1446-7256 |
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| author | Shen, K. Cantor, J. R. Wolfson, Rachel Laura Chantranupong, Lynne Saxton, Robert Andrew Scaria, Sonia M. Sabatini, David |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Shen, K. Cantor, J. R. Wolfson, Rachel Laura Chantranupong, Lynne Saxton, Robert Andrew Scaria, Sonia M. Sabatini, David |
| author_sort | Shen, K. |
| collection | MIT |
| description | Leucine is a proteogenic amino acid that also regulates many aspects of mammalian physiology, in large part by activating the mTOR complex 1 (mTORC1) protein kinase, a master growth controller. Amino acids signal to mTORC1 through the Rag guanosine triphosphatases (GTPases). Several factors regulate the Rags, including GATOR1, aGTPase-activating protein; GATOR2, a positive regulator of unknown function; and Sestrin2, a GATOR2-interacting protein that inhibits mTORC1 signaling. We find that leucine, but not arginine, disrupts the Sestrin2-GATOR2 interaction by binding to Sestrin2 with a dissociation constant of 20 micromolar, which is the leucine concentration that half-maximally activates mTORC1. The leucine-binding capacity of Sestrin2 is required for leucine to activate mTORC1 in cells. These results indicate that Sestrin2 is a leucine sensor for the mTORC1 pathway. |
| first_indexed | 2024-09-23T13:42:19Z |
| format | Article |
| id | mit-1721.1/107960 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:42:19Z |
| publishDate | 2017 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1079602022-10-01T16:40:04Z Sestrin2 is a leucine sensor for the mTORC1 pathway Shen, K. Cantor, J. R. Wolfson, Rachel Laura Chantranupong, Lynne Saxton, Robert Andrew Scaria, Sonia M. Sabatini, David Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Wolfson, Rachel Laura Chantranupong, Lynne Saxton, Robert Andrew Scaria, Sonia M. Sabatini, David Leucine is a proteogenic amino acid that also regulates many aspects of mammalian physiology, in large part by activating the mTOR complex 1 (mTORC1) protein kinase, a master growth controller. Amino acids signal to mTORC1 through the Rag guanosine triphosphatases (GTPases). Several factors regulate the Rags, including GATOR1, aGTPase-activating protein; GATOR2, a positive regulator of unknown function; and Sestrin2, a GATOR2-interacting protein that inhibits mTORC1 signaling. We find that leucine, but not arginine, disrupts the Sestrin2-GATOR2 interaction by binding to Sestrin2 with a dissociation constant of 20 micromolar, which is the leucine concentration that half-maximally activates mTORC1. The leucine-binding capacity of Sestrin2 is required for leucine to activate mTORC1 in cells. These results indicate that Sestrin2 is a leucine sensor for the mTORC1 pathway. United States. National Institutes of Health (R01CA103866) United States. National Institutes of Health (AI47389) United States. Department of Defense (W81XWH-07-0448) United States. National Institutes of Health (T32 GM007753) United States. National Institutes of Health (F30 CA189333) United States. National Institutes of Health (F31 CA180271) 2017-04-07T18:36:39Z 2017-04-07T18:36:39Z 2016-01 Article http://purl.org/eprint/type/JournalArticle 0036-8075 1095-9203 http://hdl.handle.net/1721.1/107960 Wolfson, R. L., L. Chantranupong, R. A. Saxton, K. Shen, S. M. Scaria, J. R. Cantor, and D. M. Sabatini. “Sestrin2 Is a Leucine Sensor for the mTORC1 Pathway.” Science 351, no. 6268 (October 8, 2015): 43–48. © 2016 American Association for the Advancement of Science https://orcid.org/0000-0002-9535-7664 https://orcid.org/0000-0001-9388-1633 https://orcid.org/0000-0002-9376-3984 https://orcid.org/0000-0002-1446-7256 en_US http://dx.doi.org/10.1126/science.aab2674 Science 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. application/pdf American Association for the Advancement of Science (AAAS) PMC |
| spellingShingle | Shen, K. Cantor, J. R. Wolfson, Rachel Laura Chantranupong, Lynne Saxton, Robert Andrew Scaria, Sonia M. Sabatini, David Sestrin2 is a leucine sensor for the mTORC1 pathway |
| title | Sestrin2 is a leucine sensor for the mTORC1 pathway |
| title_full | Sestrin2 is a leucine sensor for the mTORC1 pathway |
| title_fullStr | Sestrin2 is a leucine sensor for the mTORC1 pathway |
| title_full_unstemmed | Sestrin2 is a leucine sensor for the mTORC1 pathway |
| title_short | Sestrin2 is a leucine sensor for the mTORC1 pathway |
| title_sort | sestrin2 is a leucine sensor for the mtorc1 pathway |
| url | http://hdl.handle.net/1721.1/107960 https://orcid.org/0000-0002-9535-7664 https://orcid.org/0000-0001-9388-1633 https://orcid.org/0000-0002-9376-3984 https://orcid.org/0000-0002-1446-7256 |
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