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J. Biol. Chem. 286 (8): 6128-6142

© 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

Amino Acids Activate Mammalian Target of Rapamycin Complex 2 (mTORC2) via PI3K/Akt Signaling*Formula

Irantzu Tato1, Ramon Bartrons, Francesc Ventura, , and Jose Luis Rosa2

From the Departament de Ciències Fisiològiques II, Campus de Bellvitge, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona E-08907, Spain

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Abstract: The activity of mammalian target of rapamycin (mTOR) complexes regulates essential cellular processes, such as growth, proliferation, or survival. Nutrients such as amino acids are important regulators of mTOR complex 1 (mTORC1) activation, thus affecting cell growth, protein synthesis, and autophagy. Here, we show that amino acids may also activate mTOR complex 2 (mTORC2). This activation is mediated by the activity of class I PI3K and of Akt. Amino acids induced a rapid phosphorylation of Akt at Thr-308 and Ser-473. Whereas both phosphorylations were dependent on the presence of mTOR, only Akt phosphorylation at Ser-473 was dependent on the presence of rictor, a specific component of mTORC2. Kinase assays confirmed mTORC2 activation by amino acids. This signaling was functional, as demonstrated by the phosphorylation of Akt substrate FOXO3a. Interestingly, using different starvation conditions, amino acids can selectively activate mTORC1 or mTORC2. These findings identify a new signaling pathway used by amino acids underscoring the crucial importance of these nutrients in cell metabolism and offering new mechanistic insights.

Key Words: Akt PKB • Amino acid • Autophagy • mTOR • mTOR Complex (mTORC)

Received for publication July 21, 2010. Revision received November 9, 2010.


1 Supported by the Juan de la Cierva Program.

2 To whom correspondence should be addressed. Tel.: 34-934021056; Fax: 34-934024268; E-mail: joseluisrosa{at}

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