The Target of Rapamycin (TOR) protein is a Ser/Thr kinase that functions in two distinct multiprotein complexes: TORC1 and TORC2. These conserved complexes regulate many different aspects of cell growth in response to intracellular and extracellular cues. Here we report that the AGC kinase Sch9 is a substrate of yeast TORC1. Six amino acids in the C terminus of Sch9 are directly phosphorylated by TORC1. Phosphorylation of these residues is lost upon rapamycin treatment as well as carbon or nitrogen starvation and transiently reduced following application of osmotic, oxidative, or thermal stress. TORC1-dependent phosphorylation is required for Sch9 activity, and replacement of residues phosphorylated by TORC1 with Asp/Glu renders Sch9 activity TORC1 independent. Sch9 is required for TORC1 to properly regulate ribosome biogenesis, translation initiation, and entry into G0 phase, but not expression of Gln3-dependent genes. Our results suggest that Sch9 functions analogously to the mammalian TORC1 substrate S6K1 rather than the mTORC2 substrate PKB/Akt.

In all living organisms, appropriate reactions to unfavorable environmental conditions (stress factors) are observed. When transcription in eukaryotic cells is controlled by extracellular signals, at least one signaling component has to be translocated from the cytoplasm to the nucleus in a signal-dependent manner. The signaling components may be of low molecular weight (second messengers) or protein members of the signaling cascades. Examples for the latter are MAP kinases, for example, the p42 MAP kinase and p44 ERK1 on mitogenic stimulation (Chen et al. 1992).Regulated nuclear translocation is also found widely at the level of transcription factors and is achieved by either cytoplasmic anchoring or activation of nuclear localization signals (NLS) by unmasking or modification (Jans 1995;Gö rlich and Mattaj 1996;Nigg 1997). A prominent example of this type of control is provided by NF-B. A rapid transcriptional response to a variety of stress stimuli is elicited by phosphorylation of the inhibitory factor IB followed by its dissociation from the transcription factor and destruction. This leads to unmasking of the NF-B nuclear localization signal and to the subsequent translocation to the nucleus (Siebenlist, et al. 1995;Baldwin 1996). Another example is NF-ATc, a transcription factor involved in early immune responses that is translocated to the nucleus on dephosphorylation by Ca 2+

Acute stress puts cells at risk, and rapid adaptation is crucial for maximizing cell survival. Cellular adaptation mechanisms include modification of certain aspects of cell physiology, such as the induction of efficient changes in the gene expression programmes by intracellular signalling networks. Recent studies using genome-wide approaches as well as single-cell transcription measurements, in combination with classical genetics, have shown that rapid and specific activation of gene expression can be accomplished by several different strategies. This article discusses how organisms can achieve generic and specific responses to different stresses by regulating gene expression at multiple stages of mRNA biogenesis from chromatin structure to transcription, mRNA stability and translation.