Signal Specificity and Signal Integration in Filamentous Growth
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Cells utilize signal transduction pathways in order to adapt to changes in the environment. Model eukaryote Saccharomyces cerevisiae undergoes filamentous growth when nutrient sources become limiting. One of the pathways that control this response is the filamentous growth (FG) MAPK pathway. This pathway shares components with other MAPK pathways. In this study, we have uncovered a new component of the MAPK pathway, Bem4p, which may activate Cdc24p, the only known GEF for the Rho GTPase Cdc42p. I was able to characterize specific interactions with Bem4p and the PH domain of Cdc24p, which may be auto-inhibitory and is a novel interaction domain for this protein. Additionally, Bem4p interacts with other shared components in order to elicit a filamentous growth specific response. I have also shown a signal integration network during filamentous growth. A number of pathways and protein complexes have been characterized as contributing to filamentous growth, including Ras2/cAMP, Rim, and the Rpd3(L) complex. I have characterized new positive regulators of filamentous growth, including the RTG pathway and the cyclin dependent kinase Pho85p. Utilizing genetic screens as well as hypothesis based approaches, I have shown that many pathways and protein complexes that effect filamentous growth also contribute to the activation of the FG MAPK pathway. Specifically, many of these proteins effect the expression of MSB2 and/or TEC1, which are components of the pathway. These pathways and complexes are activated under different conditions, so these connections to MSB2 and TEC1 likely sensitize the MAPK pathway to a number of stimuli. By the identification of new pathway regulators, and new regulatory connections between pathways, a clearer picture emerges of MAPK pathway regulation and signal integration that may extend to other systems.