The TOR nutrient signalling pathway phosphorylates NPR1 and inhibits turnover of the tryptophan permease

Anja Schmidt, Thomas Beck, Antonius Koller, Jeannette Kunz, Michael N. Hall

Research output: Contribution to journalArticle

241 Citations (Scopus)

Abstract

The Saccharomyces cerevisiae targets of rapamycin, TOR1 and TOR2, signal activation of cell growth in response to nutrient availability. Loss of TOR or rapamycin treatment causes yeast cells to arrest growth in early G1 and to express several other physiological properties of starved (G0) cells. As part of this starvation response, high affinity amino acid permeases such as the tryptophan permease TAT2 are targeted to the vacuole and degraded. Here we show that the TOR signalling pathway phosphorylates the Ser/Thr kinase NPR1 and thereby inhibits the starvation-induced turnover of TAT2. Overexpression of NPR1 inhibits growth and induces the degradation of TAT2, whereas loss of NPR1 confers resistance to rapamycin and to FK506, an inhibitor of amino acid import. NPR1 is controlled by TOR and the type 2A phosphatase-associated protein TAP42. First, overexpression of NPR1 is toxic only when TOR function is reduced. Secondly, NPR1 is rapidly dephosphorylated in the absence of TOR. Thirdly, NPR1 dephosphorylation does not occur in a rapamycin-resistant tap42 mutant. Thus, the TOR nutrient signalling pathway also controls growth by inhibiting a stationary phase (G0) programme. The control of NPR1 by TOR is analogous to the control of p70 s6 kinase and 4E-BP1 by mTOR in mammalian cells.

Original languageEnglish
Pages (from-to)6924-6931
Number of pages8
JournalEMBO Journal
Volume17
Issue number23
Publication statusPublished - Dec 1 1998
Externally publishedYes

Fingerprint

Sirolimus
Nutrients
Food
Growth
Starvation
Yeast
Cells
70-kDa Ribosomal Protein S6 Kinases
Amino Acid Transport Systems
Protein Phosphatase 2
Cell Cycle Resting Phase
Poisons
Cell growth
Tacrolimus
Vacuoles
Phosphoric Monoester Hydrolases
Saccharomyces cerevisiae
Phosphotransferases
Yeasts
Chemical activation

Keywords

  • p70(s6k)
  • Rapamycin
  • Signal transduction
  • Starvation
  • TAP42

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

The TOR nutrient signalling pathway phosphorylates NPR1 and inhibits turnover of the tryptophan permease. / Schmidt, Anja; Beck, Thomas; Koller, Antonius; Kunz, Jeannette; Hall, Michael N.

In: EMBO Journal, Vol. 17, No. 23, 01.12.1998, p. 6924-6931.

Research output: Contribution to journalArticle

Schmidt, A, Beck, T, Koller, A, Kunz, J & Hall, MN 1998, 'The TOR nutrient signalling pathway phosphorylates NPR1 and inhibits turnover of the tryptophan permease', EMBO Journal, vol. 17, no. 23, pp. 6924-6931.
Schmidt, Anja ; Beck, Thomas ; Koller, Antonius ; Kunz, Jeannette ; Hall, Michael N. / The TOR nutrient signalling pathway phosphorylates NPR1 and inhibits turnover of the tryptophan permease. In: EMBO Journal. 1998 ; Vol. 17, No. 23. pp. 6924-6931.
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