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

Author:

Roberts Christopher J.1,Nelson Bryce2,Marton Matthew J.1,Stoughton Roland1,Meyer Michael R.1,Bennett Holly A.1,He Yudong D.1,Dai Hongyue1,Walker Wynn L.1,Hughes Timothy R.1,Tyers Mike3,Boone Charles2,Friend † Stephen H.1

Affiliation:

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.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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