Abstract:
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.
Registro:
Documento: |
Artículo
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Título: | Scaffold number in yeast signaling system sets tradeoff between system output and dynamic range |
Autor: | 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. |
Filiación: | Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Molecular Sciences Institute, Berkeley, CA 94704, United States Departamento de Fisiología, Biología Molecular Y Celular, Inst. de Fisiol., Biologia Molec. Y Neurociencias-Consejo de Invest. Cientificas Y Tec., Universidad de Buenos Aires, Ciudad Universitaria, 1428 Buenos Aires, Argentina Selventa, Cambridge, MA 02140, United States Amyris Biotechnologies, Emeryville, CA 94608, United States Healthy and Active before 5, Concord, CA 94518, United States Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, United States Renaissance Technologies, East Setauket, NY 11733, United States Department of Bioengineering, Stanford University, Stanford, CA 94305, United States Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States
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Palabras clave: | 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 |
Año: | 2011
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Volumen: | 108
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Número: | 50
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Página de inicio: | 20265
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Página de fin: | 20270
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DOI: |
http://dx.doi.org/10.1073/pnas.1004042108 |
Título revista: | Proceedings of the National Academy of Sciences of the United States of America
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Título revista abreviado: | Proc. Natl. Acad. Sci. U. S. A.
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ISSN: | 00278424
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CODEN: | PNASA
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CAS: | mitogen activated protein kinase, 142243-02-5; Pheromones; Saccharomyces cerevisiae Proteins
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Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00278424_v108_n50_p20265_Thomson |
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Citas:
---------- APA ----------
Thomson, T.M., Benjamin, K.R., Bush, A., Love, T., Pincus, D., Resnekov, O., Yu, R.C.,..., Brent, R.
(2011)
. Scaffold number in yeast signaling system sets tradeoff between system output and dynamic range. Proceedings of the National Academy of Sciences of the United States of America, 108(50), 20265-20270.
http://dx.doi.org/10.1073/pnas.1004042108---------- CHICAGO ----------
Thomson, T.M., Benjamin, K.R., Bush, A., Love, T., Pincus, D., Resnekov, O., et al.
"Scaffold number in yeast signaling system sets tradeoff between system output and dynamic range"
. Proceedings of the National Academy of Sciences of the United States of America 108, no. 50
(2011) : 20265-20270.
http://dx.doi.org/10.1073/pnas.1004042108---------- MLA ----------
Thomson, T.M., Benjamin, K.R., Bush, A., Love, T., Pincus, D., Resnekov, O., et al.
"Scaffold number in yeast signaling system sets tradeoff between system output and dynamic range"
. Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 50, 2011, pp. 20265-20270.
http://dx.doi.org/10.1073/pnas.1004042108---------- VANCOUVER ----------
Thomson, T.M., Benjamin, K.R., Bush, A., Love, T., Pincus, D., Resnekov, O., et al. Scaffold number in yeast signaling system sets tradeoff between system output and dynamic range. Proc. Natl. Acad. Sci. U. S. A. 2011;108(50):20265-20270.
http://dx.doi.org/10.1073/pnas.1004042108