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Proc Natl Acad Sci U S A


Title:Scaffold number in yeast signaling system sets tradeoff between system output and dynamic range
Author(s):Thomson TM; Benjamin KR; Bush A; Love T; Pincus D; Resnekov O; Yu RC; Gordon A; Colman-Lerner A; Endy D; Brent R;
Address:"Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"
Journal Title:Proc Natl Acad Sci U S A
Year:2011
Volume:20111123
Issue:50
Page Number:20265 - 20270
DOI: 10.1073/pnas.1004042108
ISSN/ISBN:1091-6490 (Electronic) 0027-8424 (Print) 0027-8424 (Linking)
Abstract:"Although the proteins comprising many signaling systems are known, less is known about their numbers per cell. Existing measurements often vary by more than 10-fold. Here, we devised improved quantification methods to measure protein abundances in the Saccharomyces cerevisiae pheromone response pathway, an archetypical signaling system. These methods limited variation between independent measurements of protein abundance to a factor of two. We used these measurements together with quantitative models to identify and investigate behaviors of the pheromone response system sensitive to precise abundances. The difference between the maximum and basal signaling output (dynamic range) of the pheromone response MAPK cascade was strongly sensitive to the abundance of Ste5, the MAPK scaffold protein, and absolute system output depended on the amount of Fus3, the MAPK. Additional analysis and experiment suggest that scaffold abundance sets a tradeoff between maximum system output and system dynamic range, a prediction supported by recent experiments"
Keywords:"Fluorescence Immunoblotting MAP Kinase Signaling System Models, Biological Pheromones/metabolism Saccharomyces cerevisiae/*metabolism Saccharomyces cerevisiae Proteins/*metabolism *Signal Transduction *Systems Biology;"
Notes:"MedlineThomson, Ty M Benjamin, Kirsten R Bush, Alan Love, Tonya Pincus, David Resnekov, Orna Yu, Richard C Gordon, Andrew Colman-Lerner, Alejandro Endy, Drew Brent, Roger eng P50 HG002370/HG/NHGRI NIH HHS/ R01 GM097479/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural 2011/11/25 Proc Natl Acad Sci U S A. 2011 Dec 13; 108(50):20265-70. doi: 10.1073/pnas.1004042108. Epub 2011 Nov 23"

 
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