RRC ID 32727
Author Hatano T, Morigasaki S, Tatebe H, Ikeda K, Shiozaki K.
Title Fission yeast Ryh1 GTPase activates TOR Complex 2 in response to glucose.
Journal Cell Cycle
Abstract The Target Of Rapamycin (TOR) is an evolutionarily conserved protein kinase that forms 2 distinct protein complexes referred to as TOR complex 1 (TORC1) and 2 (TORC2). Recent extensive studies have demonstrated that TORC1 is under the control of the small GTPases Rheb and Rag that funnel multiple input signals including those derived from nutritional sources; however, information is scarce as to the regulation of TORC2. A previous study using the model system provided by the fission yeast Schizosaccharomyces pombe identified Ryh1, a Rab-family GTPase, as an activator of TORC2. Here, we show that the nucleotide-binding state of Ryh1 is regulated in response to glucose, mediating this major nutrient signal to TORC2. In glucose-rich growth media, the GTP-bound form of Ryh1 induces TORC2-dependent phosphorylation of Gad8, a downstream target of TORC2 in fission yeast. Upon glucose deprivation, Ryh1 becomes inactive, which turns off the TORC2-Gad8 pathway. During glucose starvation, however, Gad8 phosphorylation by TORC2 gradually recovers independently of Ryh1, implying an additional TORC2 activator that is regulated negatively by glucose. The paired positive and negative regulatory mechanisms may allow fine-tuning of the TORC2-Gad8 pathway, which is essential for growth under glucose-limited environment.
Volume 14(6)
Pages 848-56
Published 2015-1-1
DOI 10.1080/15384101.2014.1000215
PMID 25590601
PMC PMC4612450
MeSH Amino Acid Motifs Glucose / pharmacology* Hydrophobic and Hydrophilic Interactions Mechanistic Target of Rapamycin Complex 2 Monomeric GTP-Binding Proteins / chemistry Monomeric GTP-Binding Proteins / metabolism* Multiprotein Complexes / metabolism* Nitrogen / deficiency Phosphorylation / drug effects Protein Serine-Threonine Kinases / chemistry Protein Serine-Threonine Kinases / metabolism Schizosaccharomyces / cytology Schizosaccharomyces / enzymology* Schizosaccharomyces pombe Proteins / chemistry Schizosaccharomyces pombe Proteins / metabolism* TOR Serine-Threonine Kinases / metabolism*
IF 3.699
Times Cited 22
Yeast FY13668 FY13666 FY13657 FY15942