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Bao, MZ, Schwartz, MA, Cantin, GT, Yates, JR 3rd and Madhani, HD (2004) Pheromone-dependent destruction of the Tec1 transcription factor is required for MAP kinase signaling specificity in yeast. Cell 119:991-1000
The yeast MAPK pathways required for mating versus filamentous growth share multiple components yet specify distinct programs. The mating-specific MAPK, Fus3, prevents crosstalk between the two pathways by unknown mechanisms. Here we show that pheromone signaling induces Fus3-dependent degradation of Tec1, the transcription factor specific to the filamentation pathway. Degradation requires Fus3 kinase activity and a MAPK phosphorylation site in Tec1 at threonine 273. Fus3 associates with Tec1 in unstimulated cells, and active Fus3 phosphorylates Tec1 on T273 in vitro. Destruction of Tec1 requires the F box protein Dia2 (Digs-into-agar-2), and Cdc53, the Cullin of SCF (Skp1-Cdc53-F box) ubiquitin ligases. Notably, mutation of the phosphoacceptor site in Tec1, deletion of FUS3, or deletion of DIA2 results in a loss of signaling specificity such that pheromone pathway signaling erroneously activates filamentation pathway gene expression and invasive growth. Signal-induced destruction of a transcription factor for a competing pathway provides a mechanism for signaling specificity.
Amino Acid Sequence; Cell Cycle Proteins/genetics; Cell Cycle Proteins/metabolism; Cullin Proteins/genetics; Cullin Proteins/metabolism; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; F-Box Proteins/genetics; F-Box Proteins/metabolism; MAP Kinase Signaling System/drug effects; Mitogen-Activated Protein Kinases/genetics; Mitogen-Activated Protein Kinases/metabolism; Molecular Sequence Data; Mutation; Pheromones/pharmacology; Phosphorylation/drug effects; Protein Binding/drug effects; SKP Cullin F-Box Protein Ligases/deficiency; SKP Cullin F-Box Protein Ligases/genetics; SKP Cullin F-Box Protein Ligases/metabolism; Saccharomyces cerevisiae/drug effects; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism; Substrate Specificity; Threonine/genetics; Threonine/metabolism; Transcription Factors/genetics; Transcription Factors/metabolism; Ubiquitin/genetics; Ubiquitin/metabolism; Ubiquitin-Protein Ligase Complexes/genetics; Ubiquitin-Protein Ligase Complexes/metabolism
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