Two proteins in yeast, structurally and functionally homologous to the ras family of mammalian oncoproteins, mediate initiation of the cell cycle in response to nutrient availability and regulate the developmental switch between yeast and pseudohyphal morphology. The ras pathway acts in parallel with a second pathways mediated by protein kinases, called Tor, that are targets of the anti-fungal and immunosuppressive drug, rapamycin. We will explore how the balanced activity of these two pathways regulates yeast cell growth and development, with the expectation that such studies will shed light on the mechanism by which imbalance of signaling through these pathways causes tumorigenic transformation in larger cells. We plan to investigate how these two pathways respond to nutrient availability, and how these pathways are interconnected, by dissecting specific components of the pathway and by using microarray technology to monitor cellular responses of pathway mutants. In the former approach, we conduct an extensive molecular genetic analysis of protein phosphatase 2A/Tap42-a key mediator of the Tor pathway. In addition, we are defining sensors that connect these pathways to nutrient availability. In the second approach, we are defining sensors that connect these pathways to nutrient availability. In the second approach, we are examining the global expression of yeast genes in response to nutrient transitions in a variety of mutants blocked at specific points in the signaling pathways. This allows us to define precisely the role of each of the pathways in mediating a major response of the cell to external signals and to formulate how the cell integrates information from multiple pathways to achieve a uniform and appropriate response to changing conditions.
|Effective start/end date||10/1/95 → 9/30/02|
- National Cancer Institute: $242,018.00
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