title: A role for TOR complex 2 signaling in promoting autophagy.
abstract: The conserved target of rapamycin (TOR) kinase is a central regulator of cell growth in response to nutrient availability. TOR forms 2 structurally and functionally distinct complexes, TORC1 and TORC2, and negatively regulates autophagy via TORC1. Here we demonstrate TOR also operates independently through the TORC2 signaling pathway to promote autophagy upon amino acid limitation. Under these conditions, TORC2, through its downstream target kinase Ypk1, inhibits the Ca(2+)- and Cmd1/calmodulin-dependent phosphatase, calcineurin, to enable the activation of the amino acid-sensing EIF2S1/eIF2α kinase, Gcn2, and promote autophagy. Thus TORC2 signaling regulates autophagy in a pathway distinct from TORC1 to provide a tunable response to the cellular metabolic state.
authors.affiliation: a Department of Molecular and Cellular Biology; College of Biological Sciences ; University of California, Davis ; Davis , CA USA.
authors.forename: Ariadne
authors.initials: A
authors.lastname: Vlahakis
authors.forename: Ted
authors.initials: T
authors.lastname: Powers
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D001343:Autophagy; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D018450:Disease Progression; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes / Q000378:metabolism*; D009584:Nitrogen / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3; C068124:MCK1 protein, S cerevisiae; D019703:Calcineurin; D009584:Nitrogen; D002118:Calcium
keywords: GAAC; Gcn2; Gcn4; TOR; TORC1; TORC2; Ypk1; amino acid; calcineurin; nitrogen