TOR2 Is Part of Two Related Signaling Pathways Coordinating Cell Growth in Saccharomyces cerevisiae

Corresponding author: Michael N. Hall, Department of Biochemistry, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland, hall{at}ubaclu.unibas.ch (E-mail).

Communicating editor: A. G. HINNEBUSCH

The Saccharomyces cerevisiae genes TOR1 and TOR2 encode phosphatidylinositol kinase homologs. TOR2 has two essential functions. One function overlaps with TOR1 and mediates protein synthesis and cell cycle progression. The second essential function of TOR2 is unique to TOR2 and mediates the cell-cycle-dependent organization of the actin cytoskeleton. We have isolated temperature-sensitive mutants that are defective for either one or both of the two TOR2 functions. The three classes of mutants were as follows. Class A mutants, lacking only the TOR2-unique function, are defective in actin cytoskeleton organization and arrest within two to three generations as small-budded cells in the G2/M phase of the cell cycle. Class B mutants, lacking only the TOR-shared function, and class C mutants, lacking both functions, exhibit a rapid loss of protein synthesis and a G1 arrest within one generation. To define further the two functions of TOR2, we isolated multicopy suppressors that rescue the class A or B mutants. Overexpression of MSS4, PKC1, PLC1, RHO2, ROM2, or SUR1 suppressed the growth defect of a class A mutant. Surprisingly, overexpression of PLC1 and MSS4 also suppressed the growth defect of a class B mutant. These genes encode proteins that are involved in phosphoinositide metabolism and signaling. Thus, the two functions (readouts) of TOR2 appear to involve two related signaling pathways controlling cell growth.

This article has been cited by other articles:

				C. Huttenhower and O.G. Troyanskaya Assessing the functional structure of genomic data Bioinformatics, July 1, 2008; 24(13): i330 - i338. [Abstract] [Full Text] [PDF]

				S. Aronova, K. Wedaman, S. Anderson, J. Yates III, and T. Powers Probing the Membrane Environment of the TOR Kinases Reveals Functional Interactions between TORC1, Actin, and Membrane Trafficking in Saccharomyces cerevisiae Mol. Biol. Cell, August 1, 2007; 18(8): 2779 - 2794. [Abstract] [Full Text] [PDF]

				M. Uritani, H. Hidaka, Y. Hotta, M. Ueno, T. Ushimaru, and T. Toda Fission yeast Tor2 links nitrogen signals to cell proliferation and acts downstream of the Rheb GTPase Genes Cells, December 1, 2006; 11(12): 1367 - 1379. [Abstract] [Full Text] [PDF]

				J. M. Mulet, D. E. Martin, R. Loewith, and M. N. Hall Mutual Antagonism of Target of Rapamycin and Calcineurin Signaling J. Biol. Chem., November 3, 2006; 281(44): 33000 - 33007. [Abstract] [Full Text] [PDF]

				A. Reinke, J. C.-Y. Chen, S. Aronova, and T. Powers Caffeine Targets TOR Complex I and Provides Evidence for a Regulatory Link between the FRB and Kinase Domains of Tor1p J. Biol. Chem., October 20, 2006; 281(42): 31616 - 31626. [Abstract] [Full Text] [PDF]

				S. Teichert, M. Wottawa, B. Schonig, and B. Tudzynski Role of the Fusarium fujikuroi TOR Kinase in Nitrogen Regulation and Secondary Metabolism. Eukaryot. Cell, October 1, 2006; 5(10): 1807 - 1819. [Abstract] [Full Text] [PDF]

				G. Bultynck, V. L. Heath, A. P. Majeed, J.-M. Galan, R. Haguenauer-Tsapis, and M. S. Cyert Slm1 and Slm2 Are Novel Substrates of the Calcineurin Phosphatase Required for Heat Stress-Induced Endocytosis of the Yeast Uracil Permease Mol. Cell. Biol., June 15, 2006; 26(12): 4729 - 4745. [Abstract] [Full Text] [PDF]

				F. Steinboeck, L. Krupanska, A. Bogusch, A. Kaufmann, and E. Heidenreich Novel Regulatory Properties of Saccharomyces cerevisiae Arp4. J. Biochem., April 1, 2006; 139(4): 741 - 751. [Abstract] [Full Text] [PDF]

				M. Kaeberlein, R. W. Powers III, K. K. Steffen, E. A. Westman, D. Hu, N. Dang, E. O. Kerr, K. T. Kirkland, S. Fields, and B. K. Kennedy Regulation of Yeast Replicative Life Span by TOR and Sch9 in Response to Nutrients Science, November 18, 2005; 310(5751): 1193 - 1196. [Abstract] [Full Text] [PDF]

				Y. Kamada, Y. Fujioka, N. N. Suzuki, F. Inagaki, S. Wullschleger, R. Loewith, M. N. Hall, and Y. Ohsumi Tor2 Directly Phosphorylates the AGC Kinase Ypk2 To Regulate Actin Polarization Mol. Cell. Biol., August 15, 2005; 25(16): 7239 - 7248. [Abstract] [Full Text] [PDF]

				D. E. Levin Cell Wall Integrity Signaling in Saccharomyces cerevisiae Microbiol. Mol. Biol. Rev., June 1, 2005; 69(2): 262 - 291. [Abstract] [Full Text] [PDF]

				S. A. Dames, J. M. Mulet, K. Rathgeb-Szabo, M. N. Hall, and S. Grzesiek The Solution Structure of the FATC Domain of the Protein Kinase Target of Rapamycin Suggests a Role for Redox-dependent Structural and Cellular Stability J. Biol. Chem., May 27, 2005; 280(21): 20558 - 20564. [Abstract] [Full Text] [PDF]

				T. Kobayashi, H. Takematsu, T. Yamaji, S. Hiramoto, and Y. Kozutsumi Disturbance of Sphingolipid Biosynthesis Abrogates the Signaling of Mss4, Phosphatidylinositol-4-phosphate 5-Kinase, in Yeast J. Biol. Chem., May 6, 2005; 280(18): 18087 - 18094. [Abstract] [Full Text] [PDF]

				M. Fadri, A. Daquinag, S. Wang, T. Xue, and J. Kunz 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, April 1, 2005; 16(4): 1883 - 1900. [Abstract] [Full Text] [PDF]

				H. Morales-Johansson, P. Jenoe, F. T. Cooke, and M. N. Hall Negative Regulation of Phosphatidylinositol 4,5-Bisphosphate Levels by the INP51-associated Proteins TAX4 and IRS4 J. Biol. Chem., September 17, 2004; 279(38): 39604 - 39610. [Abstract] [Full Text] [PDF]

				K. H. Cox, J. J. Tate, and T. G. Cooper Actin Cytoskeleton Is Required For Nuclear Accumulation of Gln3 in Response to Nitrogen Limitation but Not Rapamycin Treatment in Saccharomyces cerevisiae J. Biol. Chem., April 30, 2004; 279(18): 19294 - 19301. [Abstract] [Full Text] [PDF]

				A. Reinke, S. Anderson, J. M. McCaffery, J. Yates III, S. Aronova, S. Chu, S. Fairclough, C. Iverson, K. P. Wedaman, and T. Powers TOR Complex 1 Includes a Novel Component, Tco89p (YPL180w), and Cooperates with Ssd1p to Maintain Cellular Integrity in Saccharomyces cerevisiae J. Biol. Chem., April 9, 2004; 279(15): 14752 - 14762. [Abstract] [Full Text] [PDF]

				A. K.A. deHart, J. D. Schnell, D. A. Allen, J.-Y. Tsai, and L. Hicke Receptor Internalization in Yeast Requires the Tor2-Rho1 Signaling Pathway Mol. Biol. Cell, November 1, 2003; 14(11): 4676 - 4684. [Abstract] [Full Text] [PDF]

				H. Wang and Y. Jiang The Tap42-Protein Phosphatase Type 2A Catalytic Subunit Complex Is Required for Cell Cycle-Dependent Distribution of Actin in Yeast Mol. Cell. Biol., May 1, 2003; 23(9): 3116 - 3125. [Abstract] [Full Text] [PDF]

				A. L. Hughes and R. Friedman Parallel Evolution by Gene Duplication in the Genomes of Two Unicellular Fungi Genome Res., May 1, 2003; 13(5): 794 - 799. [Abstract] [Full Text] [PDF]

				J. L. Crespo and M. N. Hall Elucidating TOR Signaling and Rapamycin Action: Lessons from Saccharomyces cerevisiae Microbiol. Mol. Biol. Rev., December 1, 2002; 66(4): 579 - 591. [Abstract] [Full Text] [PDF]

				J. Torres, C. J. Di Como, E. Herrero, and M. A. de la Torre-Ruiz Regulation of the Cell Integrity Pathway by Rapamycin-sensitive TOR Function in Budding Yeast J. Biol. Chem., November 1, 2002; 277(45): 43495 - 43504. [Abstract] [Full Text] [PDF]

				S. Hohmann Osmotic Stress Signaling and Osmoadaptation in Yeasts Microbiol. Mol. Biol. Rev., June 1, 2002; 66(2): 300 - 372. [Abstract] [Full Text] [PDF]

				S.-K. Hong, M.-K. Cha, Y.-S. Choi, W.-C. Kim, and I.-H. Kim Msn2p/Msn4p Act as a Key Transcriptional Activator of Yeast Cytoplasmic Thiol Peroxidase II J. Biol. Chem., March 29, 2002; 277(14): 12109 - 12117. [Abstract] [Full Text] [PDF]

				T. Schmelzle, S. B. Helliwell, and M. N. Hall Yeast Protein Kinases and the RHO1 Exchange Factor TUS1 Are Novel Components of the Cell Integrity Pathway in Yeast Mol. Cell. Biol., March 1, 2002; 22(5): 1329 - 1339. [Abstract] [Full Text] [PDF]

				B. L. Drees, B. Sundin, E. Brazeau, J. P. Caviston, G.-C. Chen, W. Guo, K. G. Kozminski, M. W. Lau, J. J. Moskow, A. Tong, et al. A protein interaction map for cell polarity development J. Cell Biol., August 6, 2001; 154(3): 549 - 576. [Abstract] [Full Text] [PDF]

				G. J. Smits, H. van den Ende, and F. M. Klis Differential regulation of cell wall biogenesis during growth and development in yeast Microbiology, April 1, 2001; 147(4): 781 - 794. [Full Text]

				M. J. Rebecchi and S. N. Pentyala Structure, Function, and Control of Phosphoinositide-Specific Phospholipase C Physiol Rev, October 1, 2000; 80(4): 1291 - 1335. [Abstract] [Full Text] [PDF]

				N. Marcoux, S. Cloutier, E. Zakrzewska, P.-M. Charest, Y. Bourbonnais, and D. Pallotta Suppression of the Profilin-Deficient Phenotype by the RHO2 Signaling Pathway in Saccharomyces cerevisiae Genetics, October 1, 2000; 156(2): 579 - 592. [Abstract] [Full Text]

				A. Mayer, D. Scheglmann, S. Dove, A. Glatz, W. Wickner, and A. Haas Phosphatidylinositol 4,5-Bisphosphate Regulates Two Steps of Homotypic Vacuole Fusion Mol. Biol. Cell, March 1, 2000; 11(3): 807 - 817. [Abstract] [Full Text]

				P. Andrews and M. Stark Type 1 protein phosphatase is required for maintenance of cell wall integrity, morphogenesis and cell cycle progression in Saccharomyces cerevisiae J. Cell Sci., January 2, 2000; 113(3): 507 - 520. [Abstract] [PDF]

				P.-A. Delley and M. N. Hall Cell Wall Stress Depolarizes Cell Growth Via Hyperactivation of RHO1 J. Cell Biol., October 4, 1999; 147(1): 163 - 174. [Abstract] [Full Text] [PDF]

				H. Barth, M. Klingler, K. Aktories, and V. Kinzel Clostridium botulinum C2 Toxin Delays Entry into Mitosis and Activation of p34cdc2 Kinase and cdc25-C Phosphatase in HeLa cells Infect. Immun., October 1, 1999; 67(10): 5083 - 5090. [Abstract] [Full Text] [PDF]

				C. M. Alarcon, J. Heitman, and M. E. Cardenas Protein Kinase Activity and Identification of a Toxic Effector Domain of the Target of Rapamycin TOR Proteins in Yeast Mol. Biol. Cell, August 1, 1999; 10(8): 2531 - 2546. [Abstract] [Full Text]

				C. R. Nierras and J. R. Warner Protein Kinase C Enables the Regulatory Circuit That Connects Membrane Synthesis to Ribosome Synthesis in Saccharomyces cerevisiae J. Biol. Chem., May 7, 1999; 274(19): 13235 - 13241. [Abstract] [Full Text] [PDF]

				M. C. Gustin, J. Albertyn, M. Alexander, and K. Davenport MAP Kinase Pathways in the Yeast Saccharomyces cerevisiae Microbiol. Mol. Biol. Rev., December 1, 1998; 62(4): 1264 - 1300. [Abstract] [Full Text] [PDF]

				D. Zaragoza, A. Ghavidel, J. Heitman, and M. C. Schultz Rapamycin Induces the G0 Program of Transcriptional Repression in Yeast by Interfering with the TOR Signaling Pathway Mol. Cell. Biol., August 1, 1998; 18(8): 4463 - 4470. [Abstract] [Full Text]

				S. Desrivieres, F. T. Cooke, P. J. Parker, and M. N. Hall MSS4, a Phosphatidylinositol-4-phosphate 5-Kinase Required for Organization of the Actin Cytoskeleton in Saccharomyces cerevisiae J. Biol. Chem., June 19, 1998; 273(25): 15787 - 15793. [Abstract] [Full Text] [PDF]

				J. Kunz, U. Schneider, I. Howald, A. Schmidt, and M. N. Hall HEAT Repeats Mediate Plasma Membrane Localization of Tor2p in Yeast J. Biol. Chem., November 17, 2000; 275(47): 37011 - 37020. [Abstract] [Full Text] [PDF]