Genomes and Genes
Gene Symbol: TOR2
Description: phosphatidylinositol kinase-related protein kinase TOR2
Alias: DRR2, phosphatidylinositol kinase-related protein kinase TOR2
Species: Saccharomyces cerevisiae S288c
- Fadri M, Daquinag A, Wang S, Xue T, Kunz J. The pleckstrin homology domain proteins Slm1 and Slm2 are required for actin cytoskeleton organization in yeast and bind phosphatidylinositol-4,5-bisphosphate and TORC2. Mol Biol Cell. 2005;16:1883-900 pubmed..and Slm2 physically interact with Avo2 and Bit61, two components of the TORC2 signaling complex, which mediates Tor2 signaling to the actin cytoskeleton...
- deHart A, Schnell J, Allen D, Tsai J, Hicke L. Receptor internalization in yeast requires the Tor2-Rho1 signaling pathway. Mol Biol Cell. 2003;14:4676-84 pubmed..defective in ligand-stimulated internalization of the alpha-factor receptor, we identified a mutant allele of TOR2, tor2G2128R...
- Sturgill T, Cohen A, Diefenbacher M, Trautwein M, Martin D, Hall M. TOR1 and TOR2 have distinct locations in live cells. Eukaryot Cell. 2008;7:1819-30 pubmed publisher..Here, we examined the localization of green fluorescent protein (GFP) tagged, endogenous TOR1 and TOR2 in live S. cerevisiae cells...
- Schmidt A, Bickle M, Beck T, Hall M. The yeast phosphatidylinositol kinase homolog TOR2 activates RHO1 and RHO2 via the exchange factor ROM2. Cell. 1997;88:531-42 pubmedThe Saccharomyces cerevisiae phosphatidylinositol kinase homolog TOR2 is required for organization of the actin cytoskeleton...
- Aronova S, Wedaman K, Aronov P, Fontes K, Ramos K, Hammock B, et al. Regulation of ceramide biosynthesis by TOR complex 2. Cell Metab. 2008;7:148-58 pubmed publisher..Because Ypk2 is activated independently by LCBs, the direct precursors to ceramides, our data suggest a model wherein TORC2 signaling is coupled with LCB levels to control Ypk2 activity and, ultimately, regulate ceramide formation. ..
- Reinke A, Anderson S, McCaffery J, Yates J, Aronova S, Chu S, et al. TOR complex 1 includes a novel component, Tco89p (YPL180w), and cooperates with Ssd1p to maintain cellular integrity in Saccharomyces cerevisiae. J Biol Chem. 2004;279:14752-62 pubmed..Together, these results define a novel connection between TORC1 and Ssd1p-mediated maintenance of cellular integrity. ..
- Shimada K, Filipuzzi I, Stahl M, Helliwell S, Studer C, Hoepfner D, et al. TORC2 signaling pathway guarantees genome stability in the face of DNA strand breaks. Mol Cell. 2013;51:829-39 pubmed publisher..Genetic inhibition of Tor2 kinase, or its downstream effector kinases Ypk1/Ypk2, conferred similar synergistic effects in the presence of ..
- Schmidt A, Kunz J, Hall M. TOR2 is required for organization of the actin cytoskeleton in yeast. Proc Natl Acad Sci U S A. 1996;93:13780-5 pubmedThe Saccharomyces cerevisiae gene TOR2 encodes a putative phosphatidylinositol kinase that has two essential functions...
- Cardenas M, Heitman J. FKBP12-rapamycin target TOR2 is a vacuolar protein with an associated phosphatidylinositol-4 kinase activity. EMBO J. 1995;14:5892-907 pubmed..Genetic studies in yeast first implicated the TOR1 and TOR2 proteins as targets of the FKBP12-rapamycin complex...
- Schmelzle T, Helliwell S, Hall M. Yeast protein kinases and the RHO1 exchange factor TUS1 are novel components of the cell integrity pathway in yeast. Mol Cell Biol. 2002;22:1329-39 pubmed..Furthermore, our findings suggest that the YPKs are a missing link between sphingolipid signaling and the cell integrity pathway. ..
- Helliwell S, Wagner P, Kunz J, Deuter Reinhard M, Henriquez R, Hall M. TOR1 and TOR2 are structurally and functionally similar but not identical phosphatidylinositol kinase homologues in yeast. Mol Biol Cell. 1994;5:105-18 pubmedThe Saccharomyces cerevisiae genes TOR1 and TOR2 were originally identified by mutations that confer resistance to the immunosuppressant rapamycin...
- Gaubitz C, Oliveira T, Prouteau M, Leitner A, Karuppasamy M, Konstantinidou G, et al. Molecular Basis of the Rapamycin Insensitivity of Target Of Rapamycin Complex 2. Mol Cell. 2015;58:977-88 pubmed publisher..that the C-terminal part of Avo3, a subunit unique to TORC2, is close to the FKBP12-rapamycin-binding domain of Tor2. Removal of this sequence generated a FKBP12-rapamycin-sensitive TORC2 variant, which provides a powerful tool for ..
- Tu J, Song W, Carlson M. Protein phosphatase type 1 interacts with proteins required for meiosis and other cellular processes in Saccharomyces cerevisiae. Mol Cell Biol. 1996;16:4199-206 pubmed..In addition, this study indicates that the two-hybrid system offers a promising approach to understanding the multiple roles and interactions of PP1 in cellular regulation. ..
- Pracheil T, Liu Z. Tiered assembly of the yeast Far3-7-8-9-10-11 complex at the endoplasmic reticulum. J Biol Chem. 2013;288:16986-97 pubmed publisher..Our study reveals tiered assembly of the yeast Far complex at the ER and a function for Far complex's ER localization in TORC2 signaling. ..
- Jiang Y, Broach J. Tor proteins and protein phosphatase 2A reciprocally regulate Tap42 in controlling cell growth in yeast. EMBO J. 1999;18:2782-92 pubmed..These results establish Tap42 as a target of Tor and add further refinement to the Tor signaling pathway. ..
- Cardon C, Beck T, Hall M, Rutter J. PAS kinase promotes cell survival and growth through activation of Rho1. Sci Signal. 2012;5:ra9 pubmed publisher..isolated PSK1 and PSK2 in a high-copy suppressor screen of a temperature-sensitive mutant of target of rapamycin 2 (TOR2)...
- Rispal D, Eltschinger S, Stahl M, Vaga S, Bodenmiller B, Abraham Y, et al. Target of Rapamycin Complex 2 Regulates Actin Polarization and Endocytosis via Multiple Pathways. J Biol Chem. 2015;290:14963-78 pubmed publisher..Additional hits in our phosphoproteomic screens highlight the intricate control TORC2 exerts over diverse aspects of eukaryote cell physiology. ..
- Pracheil T, Thornton J, Liu Z. TORC2 signaling is antagonized by protein phosphatase 2A and the Far complex in Saccharomyces cerevisiae. Genetics. 2012;190:1325-39 pubmed publisher..Here we report that mutations in SAC7 and FAR11 suppress lethality of lst8? and TORC2-deficient (tor2-21) mutations but not TORC1 inactivation, suggesting that the essential function of Lst8 is linked only to TORC2...
- Liao H, Chen M. Target of rapamycin complex 2 signals to downstream effector yeast protein kinase 2 (Ypk2) through adheres-voraciously-to-target-of-rapamycin-2 protein 1 (Avo1) in Saccharomyces cerevisiae. J Biol Chem. 2012;287:6089-99 pubmed publisher..Together, our data support the conclusion that the direct Avo1-Ypk2 interaction is crucial for TORC2 signaling to the downstream Ypk2 pathway. ..
- Yan G, Shen X, Jiang Y. Rapamycin activates Tap42-associated phosphatases by abrogating their association with Tor complex 1. EMBO J. 2006;25:3546-55 pubmed..In addition, our data support a model in which rapamycin acts not by inhibiting the kinase activity of Tor but by disrupting its interaction with downstream targets. ..
- Beeler T, Bacikova D, Gable K, Hopkins L, Johnson C, Slife H, et al. The Saccharomyces cerevisiae TSC10/YBR265w gene encoding 3-ketosphinganine reductase is identified in a screen for temperature-sensitive suppressors of the Ca2+-sensitive csg2Delta mutant. J Biol Chem. 1998;273:30688-94 pubmed..The recombinant protein catalyzes the NADPH-dependent reduction of 3-ketosphinganine. These data indicate that Tsc10p is necessary and sufficient for catalyzing the NADPH-dependent reduction of 3-ketosphinganine to dihydrosphingosine. ..
- Lorenz M, Heitman J. TOR mutations confer rapamycin resistance by preventing interaction with FKBP12-rapamycin. J Biol Chem. 1995;270:27531-7 pubmed..Previous genetic studies in yeast identified mutations in three genes, FPR1 (FKBP12), TOR1, and TOR2, which confer rapamycin resistance, and genetic findings implicated the TOR proteins as direct targets of FKBP12-..
- Nomura W, Inoue Y. Methylglyoxal activates the target of rapamycin complex 2-protein kinase C signaling pathway in Saccharomyces cerevisiae. Mol Cell Biol. 2015;35:1269-80 pubmed publisher..Methylglyoxal activated mammalian TORC2 signaling, which, in turn, phosphorylated Akt at Ser(473). Our results suggest that methylglyoxal is a conserved initiator of TORC2 signaling among eukaryotes. ..
- Bertram P, Choi J, Carvalho J, Ai W, Zeng C, Chan T, et al. Tripartite regulation of Gln3p by TOR, Ure2p, and phosphatases. J Biol Chem. 2000;275:35727-33 pubmed..In contrast to the free Gln3p, the Ure2p-bound Gln3p is signifcantly resistant to dephosphorylation. Taken together, these results reveal a tripartite regulatory mechanism by which the phosphorylation of Gln3p is regulated. ..
- Chen E, Kaiser C. LST8 negatively regulates amino acid biosynthesis as a component of the TOR pathway. J Cell Biol. 2003;161:333-47 pubmed..Like tor2 mutants, lst8 mutants also have cell wall integrity defects...
- Mulet J, Martin D, Loewith R, Hall M. Mutual antagonism of target of rapamycin and calcineurin signaling. J Biol Chem. 2006;281:33000-7 pubmed..Thus, TORC2-SLM signaling negatively regulates calcineurin, and calcineurin negatively regulates TORC2-SLM. These findings provide a molecular basis for the mutual antagonism of growth and stress. ..
- Homza B, Vasyl kovs ka R, Semchyshyn H. [Defects in TOR regulatory complexes retard aging and carbonyl/oxidative stress development in yeast Saccharomyces cerevisiae]. Ukr Biochem J. 2014;86:85-92 pubmed..cerevisiae as compared with glucose. However, defects in TOR regulatory complexes retard aging and development of the stress in yeast independent on the type of carbohydrate in the cultivation medium. ..
- Bartlett K, Kim K. Insight into Tor2, a budding yeast microdomain protein. Eur J Cell Biol. 2014;93:87-97 pubmed publisher..compartment containing Can1 (MCC), membrane compartment containing Pma1 (MCP), and membrane compartment containing Tor2 (MCT)...
- Neklesa T, Davis R. Superoxide anions regulate TORC1 and its ability to bind Fpr1:rapamycin complex. Proc Natl Acad Sci U S A. 2008;105:15166-71 pubmed publisher..These results warrant an examination into whether similar reasons explain rapamycin resistance observed in various clinical samples. ..
- Wu G, Radwan M, Xiao M, Adachi H, Fan J, Yu Y. The TOR signaling pathway regulates starvation-induced pseudouridylation of yeast U2 snRNA. RNA. 2016;22:1146-52 pubmed publisher..The RAS/cAMP signaling pathway, which parallels the TOR pathway, plays no role in this inducible modification. ..
- Semchyshyn H, Valishkevych B. Hormetic Effect of H2O2 in Saccharomyces cerevisiae: Involvement of TOR and Glutathione Reductase. Dose Response. 2016;14:1559325816636130 pubmed publisher..reductase that suggests the enzyme involvement in the H2O2-induced hormetic response; and (4) both TOR1 and TOR2 are involved in the reciprocal regulation of the activity of glucose-6-phosphate dehydrogenase and glyoxalase 1.
- Wedaman K, Reinke A, Anderson S, Yates J, McCaffery J, Powers T. Tor kinases are in distinct membrane-associated protein complexes in Saccharomyces cerevisiae. Mol Biol Cell. 2003;14:1204-20 pubmed..That these complexes colocalize to a membrane-bound compartment suggests an intimate relationship between membrane-mediated signaling and Tor activity. ..
- Schmidt A, Schmelzle T, Hall M. The RHO1-GAPs SAC7, BEM2 and BAG7 control distinct RHO1 functions in Saccharomyces cerevisiae. Mol Microbiol. 2002;45:1433-41 pubmed..This suggests that different RHO1GAPs control different RHO1 effector pathways, thus ensuring their individual regulation at the appropriate place and time. ..
- Ho H, Lee H, Liao H, Chen M. Involvement of Saccharomyces cerevisiae Avo3p/Tsc11p in maintaining TOR complex 2 integrity and coupling to downstream signaling. Eukaryot Cell. 2008;7:1328-43 pubmed publisher..Our results also suggest that Avo2p/Slm1p-mediated signaling, but not Avo1p-mediated signaling, links to Rho1p activation specifically through the Rho1p-guanine nucleotide exchange factor Tus1p. ..
- Powers T, Walter P. Regulation of ribosome biogenesis by the rapamycin-sensitive TOR-signaling pathway in Saccharomyces cerevisiae. Mol Biol Cell. 1999;10:987-1000 pubmed..This induction has been shown previously to involve both the Ras-adenylate cyclase as well as the fermentable growth medium-induced pathways, and our results therefore suggest that these three pathways may be intimately linked. ..
- Tenay B, Kimberlin E, Williams M, Denise J, Fakilahyel J, Kim K. Inactivation of Tor proteins affects the dynamics of endocytic proteins in early stage of endocytosis. J Biosci. 2013;38:351-61 pubmedb>Tor2 is an activator of the Rom2/Rho1 pathway that regulates alpha-factor internalization...
- Noda T, Ohsumi Y. Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J Biol Chem. 1998;273:3963-6 pubmed..In nutrient-rich medium, Apg proteins are involved also in the transport of aminopeptidase I from the cytosol to the vacuole. Tor may act to switch Apg function between autophagy and transport of aminopeptidase I. ..
- Hu K, Guo S, Yan G, Yuan W, Zheng Y, Jiang Y. Ubiquitin regulates TORC1 in yeast Saccharomyces cerevisiae. Mol Microbiol. 2016;100:303-14 pubmed publisher..In an attempt to understand the role of the FRB domain in TOR function, we identified a single point mutation (Tor2(W2041R) ) in the FRB domain of Tor2 that renders yeast cells rapamycin resistant and temperature sensitive...
- Yan Y, Kang B. Regulation of Vid-dependent degradation of FBPase by TCO89, a component of TOR Complex 1. Int J Biol Sci. 2010;6:361-70 pubmed..The P1S mutation of FBPase, reported to block its degradation, was observed to impair the association of FBPase with TORCI components. These results implicated an important regulatory role of TCO89 and TORCI in this pathway. ..
- Queralt E, Igual J. Functional connection between the Clb5 cyclin, the protein kinase C pathway and the Swi4 transcription factor in Saccharomyces cerevisiae. Genetics. 2005;171:1485-98 pubmed..In summary, we report numerous genetic interactions and phenotypic descriptions supporting a close functional relationship between the Clb5 cyclin, the PKC pathway, and the Swi4 transcription factor. ..
- Morales Johansson H, Jenoe P, Cooke F, Hall M. Negative regulation of phosphatidylinositol 4,5-bisphosphate levels by the INP51-associated proteins TAX4 and IRS4. J Biol Chem. 2004;279:39604-10 pubmed..The interaction between TAX4/IRS4 and INP51 is analogous to the association of EPS15 with the 5-phosphatase synaptojanin 1 in mammalian cells, suggesting that EPS15 is an activator of synaptojanin 1. ..
- Schmidt A, Beck T, Koller A, Kunz J, Hall M. The TOR nutrient signalling pathway phosphorylates NPR1 and inhibits turnover of the tryptophan permease. EMBO J. 1998;17:6924-31 pubmedThe Saccharomyces cerevisiae targets of rapamycin, TOR1 and TOR2, signal activation of cell growth in response to nutrient availability...
- Kabir M, Kaminska J, Segel G, Bethlendy G, Lin P, Della Seta F, et al. Physiological effects of unassembled chaperonin Cct subunits in the yeast Saccharomyces cerevisiae. Yeast. 2005;22:219-39 pubmed..a wide range of abnormal phenotypes, including those caused by the diverse types of conditional mutations tor2-21, lst8-2 and rsp5-9 and those caused by the concomitant overexpression of Sit4p and Sap155p...
- Wullschleger S, Loewith R, Oppliger W, Hall M. Molecular organization of target of rapamycin complex 2. J Biol Chem. 2005;280:30697-704 pubmed..rapamycin-insensitive signaling branch and in yeast consists of the six proteins AVO1, AVO2, AVO3, BIT61, LST8, and TOR2. Here we have focused on the characterization of TORC2...
- Lin H, Choi J, Vancura A. Phosphoinositide-specific phospholipase C interacts with phosphatidylinositol kinase homolog TOR2. Biochem Biophys Res Commun. 1998;252:285-9 pubmed..The proximity of Tor2p to Plc1p may therefore result in a regulated spatial and temporal coupling of synthesis and hydrolysis of phosphorylated forms of PtdIns. ..
- McDaniel S, Hepperla A, Huang J, Dronamraju R, Adams A, Kulkarni V, et al. H3K36 Methylation Regulates Nutrient Stress Response in Saccharomyces cerevisiae by Enforcing Transcriptional Fidelity. Cell Rep. 2017;19:2371-2382 pubmed publisher..These results suggest that Set2-enforced transcriptional fidelity is critical to the proper regulation of inducible and highly regulated transcription programs. ..
- Liu Q, Ren T, Fresques T, Oppliger W, Niles B, Hur W, et al. Selective ATP-competitive inhibitors of TOR suppress rapamycin-insensitive function of TORC2 in Saccharomyces cerevisiae. ACS Chem Biol. 2012;7:982-7 pubmed publisher..cerevisiae growth. The functional target of QL-IX-55 is the ATP-binding site of TOR2 as evidenced by the discovery of resistant alleles of TOR2 through rational design and unbiased selection ..
- Yan G, Lai Y, Jiang Y. The TOR complex 1 is a direct target of Rho1 GTPase. Mol Cell. 2012;45:743-53 pubmed publisher..Our findings demonstrate that TORC1 acts both upstream and downstream of Rho1 GTPase, unveiling a mechanism that integrates stress and nutrient signals to coordinate Rho1-mediated spatial expansion and TORC1-dependent mass increase. ..
- Rai R, Varma S, Shinde N, Ghosh S, Kumaran S, Skariah G, et al. Small ubiquitin-related modifier ligase activity of Mms21 is required for maintenance of chromosome integrity during the unperturbed mitotic cell division cycle in Saccharomyces cerevisiae. J Biol Chem. 2011;286:14516-30 pubmed publisher..Our findings establish Mms21-mediated sumoylation as a determinant of cell cycle progression and maintenance of chromosome integrity during the unperturbed mitotic cell division cycle in budding yeast. ..
- Kuepfer L, Peter M, Sauer U, Stelling J. Ensemble modeling for analysis of cell signaling dynamics. Nat Biotechnol. 2007;25:1001-6 pubmed..Beyond revising our picture of TOR signaling, we expect ensemble modeling to help elucidate other insufficiently characterized cellular circuits. ..
- Baretić D, Berndt A, Ohashi Y, Johnson C, Williams R. Tor forms a dimer through an N-terminal helical solenoid with a complex topology. Nat Commun. 2016;7:11016 pubmed publisher..The spiral of one TOR interacts with the bridge of another, which together form a joint platform for the Regulatory Associated Protein of TOR (RAPTOR) regulatory subunit. ..
- LIMSON M, Sweder K. Rapamycin inhibits yeast nucleotide excision repair independently of tor kinases. Toxicol Sci. 2010;113:77-84 pubmed publisherThe yeast target of rapamycin (Tor) kinases, Tor1 and Tor2, belong to the phosphatidylinositol 3-kinase-related family of proteins, which are involved in the cellular response to DNA damage and changes in nutrient conditions...
- Stephan J, Yeh Y, Ramachandran V, Deminoff S, Herman P. The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein kinase complex to control autophagy. Proc Natl Acad Sci U S A. 2009;106:17049-54 pubmed publisher..In all, our data indicate that the PKA and Tor pathways function independently to control autophagy in S. cerevisiae, and that the Atg1/Atg13 kinase complex is a key site of signal integration within this degradative pathway. ..