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The TOR signal transduction cascade controls cellular differentiation in response to nutrients.

Publication ,  Journal Article
Cutler, NS; Pan, X; Heitman, J; Cardenas, ME
Published in: Mol Biol Cell
December 2001

Rapamycin binds and inhibits the Tor protein kinases, which function in a nutrient-sensing signal transduction pathway that has been conserved from the yeast Saccharomyces cerevisiae to humans. In yeast cells, the Tor pathway has been implicated in regulating cellular responses to nutrients, including proliferation, translation, transcription, autophagy, and ribosome biogenesis. We report here that rapamycin inhibits pseudohyphal filamentous differentiation of S. cerevisiae in response to nitrogen limitation. Overexpression of Tap42, a protein phosphatase regulatory subunit, restored pseudohyphal growth in cells exposed to rapamycin. The tap42-11 mutation compromised pseudohyphal differentiation and rendered it resistant to rapamycin. Cells lacking the Tap42-regulated protein phosphatase Sit4 exhibited a pseudohyphal growth defect and were markedly hypersensitive to rapamycin. Mutations in other Tap42-regulated phosphatases had no effect on pseudohyphal differentiation. Our findings support a model in which pseudohyphal differentiation is controlled by a nutrient-sensing pathway involving the Tor protein kinases and the Tap42-Sit4 protein phosphatase. Activation of the MAP kinase or cAMP pathways, or mutation of the Sok2 repressor, restored filamentation in rapamycin treated cells, supporting models in which the Tor pathway acts in parallel with these known pathways. Filamentous differentiation of diverse fungi was also blocked by rapamycin, demonstrating that the Tor signaling cascade plays a conserved role in regulating filamentous differentiation in response to nutrients.

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Published In

Mol Biol Cell

DOI

ISSN

1059-1524

Publication Date

December 2001

Volume

12

Issue

12

Start / End Page

4103 / 4113

Location

United States

Related Subject Headings

  • Sirolimus
  • Signal Transduction
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • Repressor Proteins
  • Receptor Protein-Tyrosine Kinases
  • Protein Phosphatase 2
  • Phosphoprotein Phosphatases
  • Nitrogen
  • Models, Biological
 

Citation

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Cutler, N. S., Pan, X., Heitman, J., & Cardenas, M. E. (2001). The TOR signal transduction cascade controls cellular differentiation in response to nutrients. Mol Biol Cell, 12(12), 4103–4113. https://doi.org/10.1091/mbc.12.12.4103
Cutler, N. S., X. Pan, J. Heitman, and M. E. Cardenas. “The TOR signal transduction cascade controls cellular differentiation in response to nutrients.Mol Biol Cell 12, no. 12 (December 2001): 4103–13. https://doi.org/10.1091/mbc.12.12.4103.
Cutler NS, Pan X, Heitman J, Cardenas ME. The TOR signal transduction cascade controls cellular differentiation in response to nutrients. Mol Biol Cell. 2001 Dec;12(12):4103–13.
Cutler, N. S., et al. “The TOR signal transduction cascade controls cellular differentiation in response to nutrients.Mol Biol Cell, vol. 12, no. 12, Dec. 2001, pp. 4103–13. Pubmed, doi:10.1091/mbc.12.12.4103.
Cutler NS, Pan X, Heitman J, Cardenas ME. The TOR signal transduction cascade controls cellular differentiation in response to nutrients. Mol Biol Cell. 2001 Dec;12(12):4103–4113.

Published In

Mol Biol Cell

DOI

ISSN

1059-1524

Publication Date

December 2001

Volume

12

Issue

12

Start / End Page

4103 / 4113

Location

United States

Related Subject Headings

  • Sirolimus
  • Signal Transduction
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • Repressor Proteins
  • Receptor Protein-Tyrosine Kinases
  • Protein Phosphatase 2
  • Phosphoprotein Phosphatases
  • Nitrogen
  • Models, Biological