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Sestrin2 is a leucine sensor for the mTORC1 pathway.


ABSTRACT: 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.

SUBMITTER: Wolfson RL 

PROVIDER: S-EPMC4698017 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Sestrin2 is a leucine sensor for the mTORC1 pathway.

Wolfson Rachel L RL   Chantranupong Lynne L   Saxton Robert A RA   Shen Kuang K   Scaria Sonia M SM   Cantor Jason R JR   Sabatini David M DM  

Science (New York, N.Y.) 20151008 6268


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 leuci  ...[more]

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