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Science 287 (5454): 873-880

Copyright © 2000 by the American Association for the Advancement of Science

Signaling and Circuitry of Multiple MAPK Pathways Revealed by a Matrix of Global Gene Expression Profiles

Christopher J. Roberts, 1* Bryce Nelson, 2* Matthew J. Marton, 1 Roland Stoughton, 1 Michael R. Meyer, 1 Holly A. Bennett, 1 Yudong D. He, 1 Hongyue Dai, 1 Wynn L. Walker, 1 Timothy R. Hughes, 1 Mike Tyers, 3 Charles Boone, 2 † Stephen H. Friend 1dagger

Genome-wide transcript profiling was used to monitor signal transduction during yeast pheromone response. Genetic manipulations allowed analysis of changes in gene expression underlying pheromone signaling, cell cycle control, and polarized morphogenesis. A two-dimensional hierarchical clustered matrix, covering 383 of the most highly regulated genes, was constructed from 46 diverse experimental conditions. Diagnostic subsets of coexpressed genes reflected signaling activity, cross talk, and overlap of multiple mitogen-activated protein kinase (MAPK) pathways. Analysis of the profiles specified by two different MAPKs--Fus3p and Kss1p--revealed functional overlap of the filamentous growth and mating responses. Global transcript analysis reflects biological responses associated with the activation and perturbation of signal transduction pathways.

1 Rosetta Inpharmatics, 12040 115th Avenue Northeast, Kirkland, WA 98034, USA.
2 Biology Department, Queen's University, Kingston, Ontario K7L 3N6, Canada.
3 Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Room 1080, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: boonec{at}biology.queensu.ca and sfriend{at}rii.com

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Fus1p Interacts With Components of the Hog1p Mitogen-Activated Protein Kinase and Cdc42p Morphogenesis Signaling Pathways to Control Cell Fusion During Yeast Mating.
B. Nelson, A. B. Parsons, M. Evangelista, K. Schaefer, K. Kennedy, S. Ritchie, T. L. Petryshen, and C. Boone (2004)
Genetics 166, 67-77
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Validation of a novel, fully integrated and flexible microarray benchtop facility for gene expression profiling.
M. Baum, S. Bielau, N. Rittner, K. Schmid, K. Eggelbusch, M. Dahms, A. Schlauersbach, H. Tahedl, M. Beier, R. Guimil, et al. (2003)
Nucleic Acids Res. 31, e151
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Identification and Characterization of a Candida albicans Mating Pheromone.
R. J. Bennett, M. A. Uhl, M. G. Miller, and A. D. Johnson (2003)
Mol. Cell. Biol. 23, 8189-8201
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Phenotypic and Transcriptional Plasticity Directed by a Yeast Mitogen-Activated Protein Kinase Network.
A. Breitkreutz, L. Boucher, B.-J. Breitkreutz, M. Sultan, I. Jurisica, and M. Tyers (2003)
Genetics 165, 997-1015
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