(528g) Invited Speaker: Developing an Omics-Based Approach to Understand and Model Eukaryotic Signal Transduction | AIChE

(528g) Invited Speaker: Developing an Omics-Based Approach to Understand and Model Eukaryotic Signal Transduction


Marten, M. - Presenter, University of Maryland, Baltimore County
Chelius, C., University of Maryland Baltimore County
Ribeiro, L., University of São Paulo
Kumar, J., University of Nebraska-Lincoln
Lincoln, S., University of Connecticut
Huso, W., University of Maryland Baltimore County
Srivastava, R., University of Connecticut
Harris, S., University of Manitoba
Eukaryotic cellular signaling networks are complex, highly interconnected systems of regulatory proteins which control nearly all biological processes. Protein post-translational modification plays a central role in these networks, and of particular interest is phosphorylation mediated by protein kinases and phosphatases. We are using both phosphoproteomic and transcriptomic approaches to study signaling pathways in the model eukaryotic organism Aspergillus nidulans. CyclicAMP-dependent protein kinase (PKA) sits at the top of a signal transduction pathway, is involved with nutrient sensing and regulation of cellular metabolism, and thus has a dramatic impact on cellular behavior. To better understand PKA systemic action, we carried out phosphoproteomic and transcriptomic differential analysis using PKA+/- strains. We identified a number of differentially phosphorylated transcription factors (TFs), most of which are of unknown function. However, one of these, CreA, is known to impact carbon catabolite repression. A phosphonull CreA mutant revealed that the down-phosphorylated site is important for CreA nuclear transport. In contrast to PKA, MpkA is the last kinase in the cell wall integrity signaling (CWIS) pathway and thus regulates far fewer genes, nominally those involved in cell wall repair. When comparing mpkA+/- strains our combined phosphoproteomic/transcriptomic data imply MpkA is involved in a number of other, previously unknown, cellular pathways including iron metabolism and morphological development. In addition to steady-state phosphorylation differences, we are examining transient phosphorylation upon CWIS perturbation. Dynamic phosphoproteomic studies are allowing us to make new connections in the signaling network, and will also allow development of a mathematical (kinetic) model composed of hundreds of coupled, ordinary differential equations. We will present preliminary dynamic results.