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

The Saccharomyces cerevisiae targets of rapamycin, TOR1 and TOR2, signal ac tivation of cell growth in response to nutrient availability. Loss of TOR o r rapamycin treatment causes yeast cells to arrest growth in early G(1) and to express several other physiological properties of starved (G(0)) cells. As part of this starvation response, high affinity amino acid permeases su ch as the tryptophan permease TAT2 are targeted to the vacuole and degraded . Here we show that the TOR signalling pathway phosphorylates the Ser/Thr k inase NPR1 and thereby inhibits the starvation-induced turnover of TAT2, Ov erexpression of NPR1 inhibits growth and induces the degradation of TAT2, w hereas loss of NPR1 confers resistance to rapamycin and to FK506, an inhibi tor of amino acid import. NPR1 is controlled by TOR and the type 2A phospha tase-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 ra pamycin-resistant tap42 mutant. Thus, the TOR nutrient signalling pathway a lso controls growth by inhibiting a stationary phase (G(0)) programme. The control of NPR1 by TOR is analogous to the control of p70 s6 kinase and 4E- BP1 by mTOR in mammalian cells.