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TOR2  -  phosphatidylinositol kinase-related...

Saccharomyces cerevisiae S288c

Synonyms: DRR2, Dominant rapamycin resistance protein 2, PI4-kinase TOR2, PI4K TOR2, Phosphatidylinositol 4-kinase TOR2, ...
 
 
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High impact information on TOR2

  • TOR2 activates this switch via ROM2, possibly via the ROM2 PH domain [1].
  • Deletion of SAC7, a gene originally identified as a suppressor of an actin mutation, also suppresses a tor2 mutation [1].
  • The Saccharomyces cerevisiae phosphatidylinositol kinase homolog TOR2 is required for organization of the actin cytoskeleton [1].
  • We now show that an intact kinase domain is required for the G1 cell cycle functions of both proteins, for the ability of a mutation in a neighboring FKBP12-rapamycin-binding domain of the TOR1 protein to inhibit the growth of yeast cells when overexpressed, and for the essential function of the TOR2 protein [2].
  • The TOR1 and TOR2 kinases (TOR) control cytoplasmic protein synthesis and degradation through the conserved TAP42 protein [3].
 

Biological context of TOR2

  • A mammalian FKBP12-rapamycin binding protein, RAFT1, shares 39% and 43% identity with TOR1 and TOR2 proteins, respectively but has not been linked to rapamycin action in vivo [4].
  • We suggest that the unique function of the phosphatidylinositol kinase homolog TOR2 is required for signaling organization of the actin cytoskeleton during the cell cycle [5].
  • TOR2, via its two functions, may thus integrate temporal and spatial control of cell growth [5].
  • Screening for multicopy suppressors of tor2, we obtained a plasmid expressing an N-terminally truncated Ypk2 protein kinase [6].
  • These findings reveal a novel function for the Tor2-Rho1 pathway in controlling endocytosis in yeast, a function that is mediated in part through the plasma membrane protein Fks1 [7].
 

Anatomical context of TOR2

  • Like tor2 mutants, lst8 mutants also have cell wall integrity defects [8].
  • We report here that the TOR2 protein is membrane associated and localized to the surface of the yeast vacuole [9].
 

Associations of TOR2 with chemical compounds

 

Physical interactions of TOR2

  • LST8 binds separately to the C-terminal kinase domain region in TOR2 and appears to modulate both the integrity and kinase activity of TORC2 [12].
  • AVO1 and AVO3 bind cooperatively to the N-terminal HEAT repeat region in TOR2 and are required for TORC2 integrity [12].
 

Enzymatic interactions of TOR2

 

Regulatory relationships of TOR2

 

Other interactions of TOR2

  • The yeast targets of FKBP12-rapamycin, TOR1 and TOR2, are large proteins with homology to lipid and protein kinases [4].
  • Receptor internalization in yeast requires the Tor2-Rho1 signaling pathway [7].
  • Formation of a ternary complex of the immunosuppressant rapamycin, its immunophilin receptor Fpr1p and Tor1p or Tor2p results in the nuclear import of several nutrient- and stress-responsive transcription factors [14].
  • The Esr1 protein was also similar to phosphatidylinositol (PI) 3-kinases, including Saccharomyces cerevisiae TOR2 (and DRR1), which are involved in G1 progression [15].
  • We found that the majority of Tor2p associates with a membrane-bound compartment along with at least four other proteins, Avo1p-Avo3p and Lst8p [16].
 

Analytical, diagnostic and therapeutic context of TOR2

References

  1. The yeast phosphatidylinositol kinase homolog TOR2 activates RHO1 and RHO2 via the exchange factor ROM2. Schmidt, A., Bickle, M., Beck, T., Hall, M.N. Cell (1997) [Pubmed]
  2. TOR kinase domains are required for two distinct functions, only one of which is inhibited by rapamycin. Zheng, X.F., Florentino, D., Chen, J., Crabtree, G.R., Schreiber, S.L. Cell (1995) [Pubmed]
  3. The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors. Beck, T., Hall, M.N. Nature (1999) [Pubmed]
  4. Mammalian RAFT1 kinase domain provides rapamycin-sensitive TOR function in yeast. Alarcon, C.M., Cardenas, M.E., Heitman, J. Genes Dev. (1996) [Pubmed]
  5. TOR2 is required for organization of the actin cytoskeleton in yeast. Schmidt, A., Kunz, J., Hall, M.N. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  6. Tor2 directly phosphorylates the AGC kinase Ypk2 to regulate actin polarization. Kamada, Y., Fujioka, Y., Suzuki, N.N., Inagaki, F., Wullschleger, S., Loewith, R., Hall, M.N., Ohsumi, Y. Mol. Cell. Biol. (2005) [Pubmed]
  7. Receptor internalization in yeast requires the Tor2-Rho1 signaling pathway. deHart, A.K., Schnell, J.D., Allen, D.A., Tsai, J.Y., Hicke, L. Mol. Biol. Cell (2003) [Pubmed]
  8. LST8 negatively regulates amino acid biosynthesis as a component of the TOR pathway. Chen, E.J., Kaiser, C.A. J. Cell Biol. (2003) [Pubmed]
  9. FKBP12-rapamycin target TOR2 is a vacuolar protein with an associated phosphatidylinositol-4 kinase activity. Cardenas, M.E., Heitman, J. EMBO J. (1995) [Pubmed]
  10. Phosphoinositide-specific phospholipase C interacts with phosphatidylinositol kinase homolog TOR2. Lin, H., Choi, J.H., Vancura, A. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  11. Identification of novel single amino acid changes that result in hyperactivation of the unique GTPase, Rheb, in fission yeast. Urano, J., Comiso, M.J., Guo, L., Aspuria, P.J., Deniskin, R., Tabancay, A.P., Kato-Stankiewicz, J., Tamanoi, F. Mol. Microbiol. (2005) [Pubmed]
  12. Molecular organization of target of rapamycin complex 2. Wullschleger, S., Loewith, R., Oppliger, W., Hall, M.N. J. Biol. Chem. (2005) [Pubmed]
  13. Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Loewith, R., Jacinto, E., Wullschleger, S., Lorberg, A., Crespo, J.L., Bonenfant, D., Oppliger, W., Jenoe, P., Hall, M.N. Mol. Cell (2002) [Pubmed]
  14. Partitioning the transcriptional program induced by rapamycin among the effectors of the Tor proteins. Shamji, A.F., Kuruvilla, F.G., Schreiber, S.L. Curr. Biol. (2000) [Pubmed]
  15. An essential gene, ESR1, is required for mitotic cell growth, DNA repair and meiotic recombination in Saccharomyces cerevisiae. Kato, R., Ogawa, H. Nucleic Acids Res. (1994) [Pubmed]
  16. Tor kinases are in distinct membrane-associated protein complexes in Saccharomyces cerevisiae. Wedaman, K.P., Reinke, A., Anderson, S., Yates, J., McCaffery, J.M., Powers, T. Mol. Biol. Cell (2003) [Pubmed]
  17. Genome-wide lethality screen identifies new PI4,5P2 effectors that regulate the actin cytoskeleton. Audhya, A., Loewith, R., Parsons, A.B., Gao, L., Tabuchi, M., Zhou, H., Boone, C., Hall, M.N., Emr, S.D. EMBO J. (2004) [Pubmed]
  18. HEAT repeats mediate plasma membrane localization of Tor2p in yeast. Kunz, J., Schneider, U., Howald, I., Schmidt, A., Hall, M.N. J. Biol. Chem. (2000) [Pubmed]
 
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