2008 OSU Molecular Life Sciences
Interdisciplinary Graduate Programs Symposium
Poster abstracts
Abstract:
Eukaryotic cells cycle between phases of cell division and quiescence in response to environmental cues like nutrient availability. The regulation of this cycling has major implications for processes such as aging, development and cancer. As in all eukaryotes, the decision to undergo cell division in the budding yeast, Saccharomyces cerevisiae, is controlled by an intricate network of signal transduction pathways. Of the known signal transduction pathways implicated in this response, the Ras/cAMP-dependent protein kinase (PKA) and TOR pathways form the focus of our studies. The TOR and Ras/PKA pathways have been shown to control a number of common functions required for proper entry into G0, including ribosome biogenesis, stress response and the regulation of the Rim15 protein kinase. While it has been suggested that the TOR pathway might signal via the PKA pathway to control several functions, like ribosomal protein expression, other studies show that the two pathways function in parallel to regulate common biological processes. Since most previous studies utilized indirect downstream reporters of signaling activity, such as changes in the transcription of target genes, we decided to use more direct approaches to study the influence of one pathway on the other. Here, we will report on studies that test the hypothesis that Ras/PKA signaling is controlled by Tor activity. For these experiments, we have used in vivo reporters of Ras/PKA signaling activity that analyze several distinct steps of this pathway, including the levels of the activated GTP-bound form of the Ras proteins and the phosphorylation state of several PKA substrates. In all, these studies indicate that the Ras/PKA pathway is not directly downstream of Tor signaling and instead suggest that a more complex feedback control mechanism exists to coordinate the activities of these two pathways.
Keywords: RasPKA, TOR, quiescence