Glutamine starvation and rapamycin inhibition of TorC1 elicit transcription of distinct groups of nitrogen‐responsive genes

Glutamine starvation, achieved by treating cells with the glutamine synthetase inhibitor methionine sulfoximine (Msx), has been envisioned to trigger dissociation of Sit4 and PP2A phosphatases from the global ser/thr kinase complex, TorC1 (Target of Rapamycin Complex 1). These freed phosphatases in turn dephosphorylate Gln3 and Gat1 thereby relocating them from the cytoplasm to the nucleus where they activate transcription of nitrogen‐regulated genes (e.g., DAL5 , DAL80 , GAT1 and GDH2 ). Phosphatase‐TorC1 dissociation can also be achieved by treating cells with the specific TorC1 inhibitor, rapamycin. The above scenario leads to the expectation that treating cells with Msx will elicit the same downstream outcomes as rapamycin treatment. In contrast to this expectation, we show that rapamycin induces high level, Gat1‐dependent expression of the DAL5 and DAL80 genes, but not that of the GDH2 or GAT1 genes. Conversely, Msx induces high level, Gln3‐dependent GDH2 and GAT1 expression, but not that of DAL5 or DAL80 . These data are more consistent with the suggestion that glutamine starvation and rapamycin inhibition of TorC1 are events that occur in parallel GATA factor‐specific regulatory pathways than they are of them being sequential events in a single pathway. They also suggest that glutamine (or glutamine metabolite) availability regulates Gln3, whereas TorC1 is the predominant regulator of Gat1.