Scaffold number in yeast signaling system sets tradeoff between system output and dynamic range

Although the proteins comprisingmany 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 pathw...

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Autores principales:	Thomson, T.M., Benjamin, K.R., Bush, A., Love, T., Pincus, D., Resnekov, O., Yu, R.C., Gordon, A., Colman-Lerner, A., Endy, D., Brent, R.
Formato:	JOUR
Materias:	Genetic algorithmic model optimization Quantitative immunoblotting Single-cell fluorescence quantification guanine nucleotide binding protein hybrid protein mitogen activated protein kinase pheromone scaffold protein article cell cycle computer model enzyme activation fluorescence genetic algorithm immunoblotting nonhuman polymerase chain reaction priority journal protein analysis quantitative analysis reporter gene Saccharomyces cerevisiae signal transduction yeast Fluorescence Immunoblotting MAP Kinase Signaling System Models, Biological Pheromones Saccharomyces cerevisiae Proteins Signal Transduction Systems Biology
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00278424_v108_n50_p20265_Thomson
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_00278424_v108_n50_p20265_Thomson
record_format	dspace
spelling	todo:paper_00278424_v108_n50_p20265_Thomson2023-10-03T14:38:05Z Scaffold number in yeast signaling system sets tradeoff between system output and dynamic range Thomson, T.M. Benjamin, K.R. Bush, A. Love, T. Pincus, D. Resnekov, O. Yu, R.C. Gordon, A. Colman-Lerner, A. Endy, D. Brent, R. Genetic algorithmic model optimization Quantitative immunoblotting Single-cell fluorescence quantification guanine nucleotide binding protein hybrid protein mitogen activated protein kinase pheromone scaffold protein article cell cycle computer model enzyme activation fluorescence genetic algorithm immunoblotting nonhuman polymerase chain reaction priority journal protein analysis quantitative analysis reporter gene Saccharomyces cerevisiae signal transduction yeast Fluorescence Immunoblotting MAP Kinase Signaling System Models, Biological Pheromones Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Signal Transduction Systems Biology Although the proteins comprisingmany 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00278424_v108_n50_p20265_Thomson
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Genetic algorithmic model optimization Quantitative immunoblotting Single-cell fluorescence quantification guanine nucleotide binding protein hybrid protein mitogen activated protein kinase pheromone scaffold protein article cell cycle computer model enzyme activation fluorescence genetic algorithm immunoblotting nonhuman polymerase chain reaction priority journal protein analysis quantitative analysis reporter gene Saccharomyces cerevisiae signal transduction yeast Fluorescence Immunoblotting MAP Kinase Signaling System Models, Biological Pheromones Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Signal Transduction Systems Biology
spellingShingle	Genetic algorithmic model optimization Quantitative immunoblotting Single-cell fluorescence quantification guanine nucleotide binding protein hybrid protein mitogen activated protein kinase pheromone scaffold protein article cell cycle computer model enzyme activation fluorescence genetic algorithm immunoblotting nonhuman polymerase chain reaction priority journal protein analysis quantitative analysis reporter gene Saccharomyces cerevisiae signal transduction yeast Fluorescence Immunoblotting MAP Kinase Signaling System Models, Biological Pheromones Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Signal Transduction Systems Biology Thomson, T.M. Benjamin, K.R. Bush, A. Love, T. Pincus, D. Resnekov, O. Yu, R.C. Gordon, A. Colman-Lerner, A. Endy, D. Brent, R. Scaffold number in yeast signaling system sets tradeoff between system output and dynamic range
topic_facet	Genetic algorithmic model optimization Quantitative immunoblotting Single-cell fluorescence quantification guanine nucleotide binding protein hybrid protein mitogen activated protein kinase pheromone scaffold protein article cell cycle computer model enzyme activation fluorescence genetic algorithm immunoblotting nonhuman polymerase chain reaction priority journal protein analysis quantitative analysis reporter gene Saccharomyces cerevisiae signal transduction yeast Fluorescence Immunoblotting MAP Kinase Signaling System Models, Biological Pheromones Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Signal Transduction Systems Biology
description	Although the proteins comprisingmany 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.
format	JOUR
author	Thomson, T.M. Benjamin, K.R. Bush, A. Love, T. Pincus, D. Resnekov, O. Yu, R.C. Gordon, A. Colman-Lerner, A. Endy, D. Brent, R.
author_facet	Thomson, T.M. Benjamin, K.R. Bush, A. Love, T. Pincus, D. Resnekov, O. Yu, R.C. Gordon, A. Colman-Lerner, A. Endy, D. Brent, R.
author_sort	Thomson, T.M.
title	Scaffold number in yeast signaling system sets tradeoff between system output and dynamic range
title_short	Scaffold number in yeast signaling system sets tradeoff between system output and dynamic range
title_full	Scaffold number in yeast signaling system sets tradeoff between system output and dynamic range
title_fullStr	Scaffold number in yeast signaling system sets tradeoff between system output and dynamic range
title_full_unstemmed	Scaffold number in yeast signaling system sets tradeoff between system output and dynamic range
title_sort	scaffold number in yeast signaling system sets tradeoff between system output and dynamic range
url	http://hdl.handle.net/20.500.12110/paper_00278424_v108_n50_p20265_Thomson
work_keys_str_mv	AT thomsontm scaffoldnumberinyeastsignalingsystemsetstradeoffbetweensystemoutputanddynamicrange AT benjaminkr scaffoldnumberinyeastsignalingsystemsetstradeoffbetweensystemoutputanddynamicrange AT busha scaffoldnumberinyeastsignalingsystemsetstradeoffbetweensystemoutputanddynamicrange AT lovet scaffoldnumberinyeastsignalingsystemsetstradeoffbetweensystemoutputanddynamicrange AT pincusd scaffoldnumberinyeastsignalingsystemsetstradeoffbetweensystemoutputanddynamicrange AT resnekovo scaffoldnumberinyeastsignalingsystemsetstradeoffbetweensystemoutputanddynamicrange AT yurc scaffoldnumberinyeastsignalingsystemsetstradeoffbetweensystemoutputanddynamicrange AT gordona scaffoldnumberinyeastsignalingsystemsetstradeoffbetweensystemoutputanddynamicrange AT colmanlernera scaffoldnumberinyeastsignalingsystemsetstradeoffbetweensystemoutputanddynamicrange AT endyd scaffoldnumberinyeastsignalingsystemsetstradeoffbetweensystemoutputanddynamicrange AT brentr scaffoldnumberinyeastsignalingsystemsetstradeoffbetweensystemoutputanddynamicrange
_version_	1782025065689251840

Scaffold number in yeast signaling system sets tradeoff between system output and dynamic range

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