Skip to main content
SpringerLink
Log in

The Role of Phosphatases in TOR Signaling in Yeast

  • Chapter
TOR

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 279))

Abstract

The TOR pathway controls cellular functions necessary for cell growth and proliferation of yeast and larger eukaryotes. The search for members of the TOR signaling cascade in yeast led to the discovery of type 2A protein phosphatases (PP2A) as important players within the pathway. We describe the roles in yeast of PP2A and the closely related phosphatase, Sit4, and then focus on complexes formed between the catalytic subunit of these phosphatases and Tap42, a direct target of the Tor protein kinases in yeast. Recent results suggest that Tap42 mediates many of the Tor functions in yeast, especially those involved in transcriptional modulation. However, whether Tap42 executes its function by inhibiting phosphatase activity or by activating phosphatases is still uncertain. In addition, Tor affects some transcriptional and physiological processes through Tap42 independent pathways. Thus, Tor proteins use multiple mechanisms to regulate transcriptional and physiological processes in yeast.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Beck, T, and Hall, M.N. (1999) The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors. Nature 402, 689–692

    Article  PubMed  CAS  Google Scholar 

  • Beck, T., Schmidt, A., and Hall, M.N. (1999) Starvation induces vacuolar targeting and degradation of the tryptophan permease in yeast. J. Cell Biol. 146, 1227–1238

    Article  PubMed  CAS  Google Scholar 

  • Booher, R.N., Deshaies, R.J., and Kirschner M.W. (1993) Properties of Saccharomyces cerevisiae weel and its differential regulation of p34CDC28 in response to G1 and G2 cyclins. EMBO J. 12, 3417–3426

    PubMed  CAS  Google Scholar 

  • Cardenas, M.E., Cutler, N.S., Lorenz, M.C., Di Como, C.J., and Heitman, J. (1999) The TOR signaling cascade regulates gene expression in response to nutrients. Genes Dev. 13, 3271–3279

    Article  PubMed  CAS  Google Scholar 

  • Chen, J., Peterson, R.T., and Schreiber, S.L. (1998) α4 associates with protein phosphatases 2A, 4 and 6. Biochem. Biophys. Res. Commun. 247, 827–832

    Article  PubMed  CAS  Google Scholar 

  • Chung, H., Nairn, A.C., Murata, K., and Brautigan, D.L. (1999) Mutation of Tyr307 and Leu309 in the protein phosphatase 2A catalytic subunit favors association with the α4 subunit which promotes dephosphorylation of elongation factor-2. Biochemistry 38, 10371–10376

    Article  PubMed  CAS  Google Scholar 

  • Cutler, N.S., Pan, X., Heitman, J., and Cardenas, M.E. (2001) The TOR signal transduction cascade controls cellular differentiation in response to nutrients. Mol. Biol. Cell 12, 4103–4113

    PubMed  CAS  Google Scholar 

  • Di Como, C.J., and Arndt, K.T. (1996) Nutrients, via the Tor proteins, stimulate the association of Tap42 with type 2A phosphatases. Genes Dev. 10, 1904–1916

    Article  PubMed  Google Scholar 

  • Diivel, K., Santhanam, A., Garrett, S., Schneper, L., and Broach, J.R. (2003) Multiple roles of Tap42 in mediating rapamycin-induced transcriptional changes in yeast. Mol. Cell II, 1467–1478

    Google Scholar 

  • Evangelista, C.C. Jr., Rodriguez Torres, A.M., Limbach, M.P., and Zitomer, R.S. (1996) Rox3 and Rts1 function in the global stress response pathway in baker’s yeast. Genetics 142, 1083–1093

    PubMed  CAS  Google Scholar 

  • Evans, D.R., and Stark, M.J. (1997) Mutations in the Saccharomyces cerevisiae type 2A protein phosphatase catalytic subunit reveal roles in cell wall integrity, actin cytoskeleton organization and mitosis. Genetics 145, 227–241

    PubMed  CAS  Google Scholar 

  • Fernandez-Sarabia, M.J., Sutton, A., Zhong, T, and Arndt, K.T. (1992) SIT4 protein phosphatase is required for the normal accumulation of SWI4, CLN1, CLN2, and HCS26 RNAs during late G1. Genes Dev. 6, 2417–2428

    Article  PubMed  CAS  Google Scholar 

  • Gancedo, J.M. (2001) Control of pseudohyphae formation in Saccharomyces cerevisiae. FEMS Microbiol. Rev. 25, 107–123

    Article  PubMed  CAS  Google Scholar 

  • Grenson, M. (1983) Study of the positive control of the general amino-acid permease and other ammonia-sensitive uptake systems by the product of the NPR1 gene in the yeast Saccharomyces cerevisaie. Eur. J. Biochem. 133, 141–144

    Article  PubMed  CAS  Google Scholar 

  • Grooves, M.R., Hanlon, N., Turowski, P., Hemmings, B.A., and Bradford D. (1999) The structure of the protein phosphatase 2A PC65/A subunit reveals the confirmation of its 15 tandemly repeats HEAT motifs. Dell 96, 99–110

    Google Scholar 

  • Hardwick, J.S., Kuruvilla, EG., Tong, J.K., Shamji, A.F., and Schreiber, S.L. (1999) Ra-pamycin-modulated transcription defines the subset of nutrient-sensitive signaling pathways directly controlled by the Tor proteins. Proc. Natl. Acad. Sci. USA 96, 14866–14870.

    Article  PubMed  CAS  Google Scholar 

  • Healy, A.M., Zolnierowicz, S., Stapleton, A.E., Goebl, M., DePaoli-Roach, A.A., and Pringle, J.R. (1991) CDC55, a Saccharomyces cerevisiae gene involved in cellular morphogenesis: identification, characterization, and homology to the B subunit of mammalian type 2 A protein phosphatase. Mol. Cell. Biol. 11, 5767–5780

    PubMed  CAS  Google Scholar 

  • Jacinto, E., Guo, B., Arndt, K.T, Schmelzle, T, and Hall, M.N. (2001) TIP41 interacts with TAP42 and negatively regulates the TOR signaling pathway. Mol. Cell 8, 1017–1026

    Article  PubMed  CAS  Google Scholar 

  • Jiang, Y., and Broach, J.R. (1999) Tor proteins and protein phosphatase 2A reciprocally regulate Tap42 in controlling cell growth in yeast. EMBO J. 18, 2782–2792

    Article  PubMed  CAS  Google Scholar 

  • Kamada, Y., Funakoshi, T, Shintani, T, Nagano, K., Ohsumi, M., and Ohsumi, Y. (2000) Tor-mediated induction of autophagy via an Apgl protein kinase complex. J. Cell. Biol. 150, 1507–1513

    Article  PubMed  CAS  Google Scholar 

  • Kornitzer, D., Sharf, R., and Kleinberger, T. (2001) Adenovirus E4orf4 protein induces PP2A-dependent growth arrest in Saccharomyces cerevisiae and interacts with the anaphase-promoting complex/cyclosome. J. Cell. Biol. 154, 331–344

    Article  PubMed  CAS  Google Scholar 

  • Kuwahara, K., Matsuo, T, Nomura, J., Igarashi, H., Kimoto, M., Inui, S., and Sakaguchi, N. (1994) Identification of a 52-kDa molecule (p52) coprecipitated with the Ig receptor-related MB-1 protein that is inducibly phosphorylated by the stimulation with phorbol myristate acetate. J. Immunol. 152, 2742–2752

    PubMed  CAS  Google Scholar 

  • Lin, F.C., and Arndt, K.T. (1995) The role of Saccharomyces cerevisiae type 2A phosphatase in the actin cytoskeleton and in entry into mitosis. EMBO J. 14, 2745–2759

    PubMed  CAS  Google Scholar 

  • Lorenz, M.C., and Heitman, J. (1998) The MEP2 ammonium permease regulates pseudohyphal differentiation in Saccharomyces cerevisiae. EMBO J. 17, 1236–1247

    Article  PubMed  CAS  Google Scholar 

  • Luke, M.M., Delia Seta, R, Di Como, C.J., Sugimoto, H., Kobayashi, R., and Arndt, K.T. (1996) The SAPs, a new family of proteins, associate and function positively with the SIT4 phosphatase. Mol. Cell. Biol. 16, 2744–2755

    PubMed  CAS  Google Scholar 

  • Masuda, C.A., Ramírez, J., Peña, A., and Montero-Lomelí, M. (2000) Regulation of monovalent ion homeostasis and pH by the Ser-Thr protein phosphatase SIT4 in Saccharomyces cerevisiae. J. Biol. Chem. 40, 30957–30961

    Article  Google Scholar 

  • Minshull, J., Straight, A., Rudner, A.D., Dernburg A.F., Belmont, A., and Murray A.W. (1996) Protein phosphatase 2A regulates MPF activity and sister chromatid cohesion in budding yeast. Curr. Biol. 6, 1609–1620

    Article  PubMed  CAS  Google Scholar 

  • Murata, K., Wu, J., and Brautigan, D.L. (1997) B cell receptor-associated protein α4 displays rapamycin-sensitive binding directly to the catalytic subunit of protein phosphatase 2A. Proc. Natl. Acad. Sci. USA 94, 10624–10629

    Article  PubMed  CAS  Google Scholar 

  • Nanahoshi, M., Nishiuma, T, Tsujishita, Y., Hara, K., Inui, S., Sakaguchi, N., and Yonezawa, K. (1998) Regulation of protein phosphatase 2A catalytic activity by al-pha4 protein and its yeast homolog Tap42. Biochem. Biophys. Res. Commun. 251, 520–526

    Article  PubMed  CAS  Google Scholar 

  • Noda, T, and Ohsumi, Y. (1998) Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J. Biol. Chem. 273, 3963–3966

    Article  PubMed  CAS  Google Scholar 

  • Pan, X., Harashima, T, and Heitman, J. (2000) Signal transduction cascades regulating pseudohyphal differentiation of Saccharomyces cerevisiae. Curr. Opin. Microbiol. 3, 567–572

    Article  PubMed  CAS  Google Scholar 

  • Peterson, R.T, Desai, B.N., Hardwick, J.S., and Schreiber, S.L. (1999) Protein phosphatase 2A interacts with the 70-kDa S6 kinase and is activated by inhibition of FKBP12-rapamycin-assocoated protein. Proc. Natl. Acad. Sci. USA 96, 4438–4442

    Article  PubMed  CAS  Google Scholar 

  • Ronne, H., Carlberg, M., Hu, G.Z., and Nehlin, J.O. (1991) Protein phosphatase 2A in Saccharomyces cerevisiae: effects on cell growth and bud morphogenesis. Mol. Cell. Biol. 11,4876-4884

    PubMed  CAS  Google Scholar 

  • Schmidt, A., Beck, T, Koller, A., Kunz, J., and Hall, M.N. (1998) The TOR nutrient signalling pathway phosphorylates NPR1 and inhibits turnover of the tryptophan permease. EMBO J. 17, 6924–6931

    Article  PubMed  CAS  Google Scholar 

  • Shamji, A.F., Kuruvilla, EG., and Schreiber, S.L. (2000) Partitioning the transcriptional program induced by rapamycin among the effectors of the Tor proteins. Curr. Biol. 10, 1574–1581

    Article  PubMed  CAS  Google Scholar 

  • Shu, Y., and Hallberg, R.L. (1995) SCS1, a multicopy suppressor of hsp60-ts mutant alleles, does not encode a mitochondrially targeted protein. Mol. Cell. Biol. 15, 5618–5626

    PubMed  CAS  Google Scholar 

  • Shu, Y., Yang, H., Hallberg, E., and Hallberg, R. (1997) Molecular genetic analysis of Rts1p, a B’ regulatory subunit of Saccharomyces cerevisiae protein phosphatase 2A. Mol. Cell. Biol. 17, 3242–3253

    PubMed  CAS  Google Scholar 

  • Springael, J.Y., and André, B. (1998) Nitrogen-regulated ubiquitination of the Gapl permease of Saccharomyces cerevisiae. Mol. Biol. Cell 9, 1253–1263

    PubMed  CAS  Google Scholar 

  • Stanbrough, M., and Magasanik, B. (1995) Transcriptional and posttranslational regulation of the general amino acid permease of Saccharomyces cerevisiae. J. Bacteriol. 177, 94–102

    PubMed  CAS  Google Scholar 

  • Sutton, A., Immanuel, D., and Arndt, K.T. (1991) The SIT4 protein phosphatase functions in late G1 for progression into S phase. Mol. Cell. Biol. 11, 2133–2148

    PubMed  CAS  Google Scholar 

  • Uesono, Y., Toh-e, A., and Kikuchi, Y. (1997) Ssd1p of Saccharomyces cerevisiae associates with RNA. J. Biol. Chem. 272, 16103–16109

    Article  PubMed  CAS  Google Scholar 

  • van Zyl, W., Huang, W., Sneddon, A.A., Stark, M., Carnier, S., Werner, M., Marck, C, Sentenac, A., and Broach, J.R. (1992) Inactivation of the protein phosphatase 2A regulatory subunit A results in morphological and transcriptional defects in Saccharomyces cerevisiae. Mol. Cell. Biol. 12, 4946–4959

    PubMed  Google Scholar 

  • Wang, Y., and Burke, D.J. (1997) Cdc55p, the B-type regulatory subunit of protein phosphatase 2A, has multiple functions in mitosis and is required for the kineto-chore/spindle checkpoint in Saccharomyces cerevisiae. Mol. Cell. Biol. 17, 620–626

    PubMed  CAS  Google Scholar 

  • Yang, H., Jiang, W., Gentry, M., and Hallberg, R.L. (2000) Loss of a protein phosphatase 2A regulatory subunit (Cdc55p) elicits improper regulation of Swelp degradation. Mol. Cell. Biol. 20, 8143–8156

    Article  PubMed  CAS  Google Scholar 

  • Zhao, Y., Boguslawski, G., Zitomer, R.S., and DePaoli-Roach, A.A. (1997) Saccharomyces cerevisiae homologs of mammalian B and B’ subunits of protein phosphatase 2A direct the enzyme to distinct cellular functions. J. Biol. Chem. 272, 8256–8262

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Biology, Princeton University, Princeton, NJ, 08544, USA

    K. Düvel & J. R. Broach

Authors
  1. K. Düvel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. R. Broach
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Friedrich-Miescher-Institute, Maulbeerstrasse 66, 4058, Basel, Switzerland

    George Thomas

  2. Whitehead Institute, 9 Cambridge Center, Cambridge, MA, 02142, USA

    David M. Sabatini MD, PhD

  3. Biozentrum, University of Basel, Klingelbergstrasse 70, 4056, Basel, Switzerland

    Michael N. Hall

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Düvel, K., Broach, J.R. (2004). The Role of Phosphatases in TOR Signaling in Yeast. In: Thomas, G., Sabatini, D.M., Hall, M.N. (eds) TOR. Current Topics in Microbiology and Immunology, vol 279. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18930-2_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-18930-2_2

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-62360-8

  • Online ISBN: 978-3-642-18930-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation