The TOR nutrient signalling pathway phosphorylates NPR1 and inhibits turnover of the tryptophan permease.
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.
Schmidt
A
A
Department of Biochemistry, Biozentrum, University of Basel, CH-4056 Basel, Switzerland.
Beck
T
T
Koller
A
A
Kunz
J
J
Hall
M N
MN
D048868:Adaptor Proteins, Signal Transducing; D026905:Amino Acid Transport Systems; D018797:Cell Cycle Proteins; D029968:Escherichia coli Proteins; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D026905:Amino Acid Transport Systems; D018797:Cell Cycle Proteins; D029968:Escherichia coli Proteins; D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D029701:Saccharomyces cerevisiae Proteins; C100984:TAP42 protein, S cerevisiae; C429825:TAT2 protein, S cerevisiae; C066958:NPR1 protein, S cerevisiae; C035131:TnaB protein, E coli; C083324:TOR1 protein, S cerevisiae; C081135:TOR2 protein, S cerevisiae