PMID:28057755

Citation	Yuan, W, Guo, S, Gao, J, Zhong, M, Yan, G, Wu, W, Chao, Y and Jiang, Y (2017) General Control Nonderepressible 2 (GCN2) Kinase Inhibits Target of Rapamycin Complex 1 in Response to Amino Acid Starvation in Saccharomyces cerevisiae. J. Biol. Chem. 292:2660-2669
Abstract	In eukaryotic cells, two conserved protein kinases, Gcn2 and TOR complex 1 (TORC1), couple amino acid conditions to protein translation. Gcn2 functions as an amino acid sensor and is activated by uncharged tRNAs that accumulate when intracellular amino acids are limited. Activated Gcn2 phosphorylates and inhibits eukaryotic initiation factor-2α (eIF2α), resulting in repression of general protein synthesis. Like Gcn2, TORC1 is also involved in sensing amino acid conditions. However, the underlying mechanism remains unclear. In the present study, we show that TORC1 is a direct target of Gcn2 kinase in the yeast Saccharomyces cerevisiae In response to amino acid starvation, Gcn2 binds to TORC1 and phosphorylates Kog1, the unique regulatory subunit of TORC1, resulting in down-regulation of TORC1 kinase activity. In the absence of Gcn2, TORC1 signaling activity increases and becomes unresponsive to amino acid starvation. Our findings demonstrate that TORC1 is an effector of Gcn2 in amino acid signaling, hence defining a novel mechanism by which TORC1 senses amino acid starvation.
Links	PubMed PMC5314164 Online version:10.1074/jbc.M116.772194
Keywords	Amino Acids/metabolism; Down-Regulation; Membrane Proteins/metabolism; Protein Binding; Protein-Serine-Threonine Kinases/metabolism; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
YEAST:GCN2	involved_in	GO:0006468: protein phosphorylation	ECO:0000314: direct assay evidence used in manual assertion		P	has_direct_input:(UniProtKB:P38873)	Seeded From UniProt	complete
YEAST:GCN2	involved_in	GO:0006468: protein phosphorylation	ECO:0000315: mutant phenotype evidence used in manual assertion		P	has_direct_input:(UniProtKB:P38873)	Seeded From UniProt	complete
YEAST:GCN2	enables	GO:0004672: protein kinase activity	ECO:0000315: mutant phenotype evidence used in manual assertion		F	has_direct_input:(UniProtKB:P38873)	Seeded From UniProt	complete
YEAST:GCN2	enables	GO:0004672: protein kinase activity	ECO:0000314: direct assay evidence used in manual assertion		F	has_direct_input:(UniProtKB:P38873)	Seeded From UniProt	complete
YEAST:GCN2	involved_in	GO:0016239: positive regulation of macroautophagy	ECO:0000314: direct assay evidence used in manual assertion		P	part_of:(GO:1990928)	Seeded From UniProt	complete
YEAST:GCN2	involved_in	GO:0100002: negative regulation of protein kinase activity by protein phosphorylation	ECO:0000314: direct assay evidence used in manual assertion		P	happens_during:(GO:1990928) has_input:(GO:0031931)	Seeded From UniProt	complete
YEAST:GCN2	involved_in	GO:1904262: negative regulation of TORC1 signaling	ECO:0000315: mutant phenotype evidence used in manual assertion		P	happens_during:(GO:1990928)	Seeded From UniProt	complete
YEAST:GCN2		GO:0004860: protein kinase inhibitor activity	ECO:0000315:		F		S. Cerevisiae, GCN2 Figure 3 shows that GCN2 inhibits TORC activity. Figure 5 shows the down-regulation of Kinase activity by GCN2.	complete CACAO 12945

References

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