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  TOR complex 2-Ypk1 signaling is an essential positive regulator of the general amino acid control response and autophagy

Vlahakis, A., Graef, M., Nunnari, J., & Powers, T. (2014). TOR complex 2-Ypk1 signaling is an essential positive regulator of the general amino acid control response and autophagy. Proc Natl Acad Sci U S A, 111(29), 10586-91. doi:10.1073/pnas.1406305111.

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 Creators:
Vlahakis, A.1, Author
Graef, M.1, Author
Nunnari, J.1, Author
Powers, T.1, Author
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1Max Planck Institute for Biology of Ageing, Max Planck Society, Joseph-Stelzmann-Str. 9b, D-50931 Cologne, DE, ou_1942284              

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Free keywords: Amino Acids/*pharmacology Autophagy/*drug effects Calcineurin/metabolism Glycogen Synthase Kinase 3/*metabolism Models, Biological Multiprotein Complexes/*metabolism Saccharomyces cerevisiae/cytology/*enzymology Saccharomyces cerevisiae Proteins/*metabolism Signal Transduction/*drug effects TOR Serine-Threonine Kinases/*metabolism
 Abstract: The highly conserved Target of Rapamycin (TOR) kinase is a central regulator of cell growth and metabolism in response to nutrient availability. TOR functions in two structurally and functionally distinct complexes, TOR Complex 1 (TORC1) and TOR Complex 2 (TORC2). Through TORC1, TOR negatively regulates autophagy, a conserved process that functions in quality control and cellular homeostasis and, in this capacity, is part of an adaptive nutrient deprivation response. Here we demonstrate that during amino acid starvation TOR also operates independently as a positive regulator of autophagy through the conserved TORC2 and its downstream target protein kinase, Ypk1. Under these conditions, TORC2-Ypk1 signaling negatively regulates the Ca(2+)/calmodulin-dependent phosphatase, calcineurin, to enable the activation of the amino acid-sensing eIF2alpha kinase, Gcn2, and to promote autophagy. Our work reveals that the TORC2 pathway regulates autophagy in an opposing manner to TORC1 to provide a tunable response to cellular metabolic status.

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 Dates: 2014
 Publication Status: Published in print
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 Identifiers: Other: 25002487
DOI: 10.1073/pnas.1406305111
ISSN: 1091-6490 (Electronic)0027-8424 (Linking)
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Title: Proc Natl Acad Sci U S A
Source Genre: Journal
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Pages: - Volume / Issue: 111 (29) Sequence Number: - Start / End Page: 10586 - 91 Identifier: -