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This proposal presentation by Kengo Watanabe focuses on the intricate signaling pathways in yeast cells, particularly the stress-responsive Mitogen-Activated Protein Kinase (MAPK) pathways. It explores how distinct signaling mechanisms—such as ROS, UV stress, osmotic stress, and more—enable specificity between MAPK pathways, building on past research by McClean et al. and Patterson et al. The goal is to assess the validity of these models and investigate the parameters that allow for effective signal discrimination in yeast.
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Specificity between two yeast MAPK pathways 120802 CSHL CCB program Project Proposal Presentation Kengo Watanabe Cell Signaling, Grad. Sch. Pharmaceut. Sci., Univ. of Tokyo, Japan
Many complicated signals go around in cell. http://en.wikipedia.org/wiki/MAPK/ERK_pathway
Many complicated signals go around in cell. http://en.wikipedia.org/wiki/MAPK/ERK_pathway
Stress-responsive Mitogen-Activated Protein Kinase (MAPK) pathway ROS, UV, Osmotic stress, Heat, Bacterial Infection, etc. Stress MAP3K MAPK pathway Cell MAP2K MAPK Apoptosis, Inflammation, Cell swelling/shrinkage, etc. Response
Each phosphorylation reaction = Michaelis-Menten equation Stress P P P Activated!! MAP3K MAP2K MAPK MAP3K MAP2K MAPK Michaelis-menten equation Activated!! Activated!! Response
Pheromone pathway & High-osmolarity pathway Yeast!! http://es.wikipedia.org/wiki/Saccharomyces_cerevisiae MAP3K MAP2K MAPK McClean M.N., et al.Nat Genet.,39, 2007 Why cross-talk is NOT occurred?
The models of McCleanet al. “Cross-talk and decision making in MAP kinase pathways.”McClean M.N., et al.Nat. Genet.,39, 2007
Simultaneous stimuli enables us to distinguish between two pathways Cross-talk Only Y3 activation Only X3 activation Switch-like Bistable
McClean group concluded “mutual inhibition” achieved the specificity. RFP = Signal2 pathway activation GFP = Signal1 pathway activation
Patterson et al. insisted “insulation”, not “mutual inhibition” achieved. “Single-cell analysis reveals that insulation maintains signaling specificity between two yeast MAPK pathways with common components.”Patterson J.C., et al.Sci. Signal.,19, 2010
Future Plan Reproduction of McClean’s model Change their model Explain Patterson’s result