Sestrin2 is a leucine sensor for the mTORC1 pathway
Author(s)Shen, K.; Cantor, J. R.; Wolfson, Rachel Laura; Chantranupong, Lynne; Saxton, Robert Andrew; Scaria, Sonia M.; Sabatini, David; ... Show more Show less
MetadataShow full item record
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.
DepartmentInstitute for Medical Engineering and Science; David H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Biology
American Association for the Advancement of Science (AAAS)
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
Author's final manuscript