Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Anaphase-Promoting Complex-Cyclosome
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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Cullin Proteins / genetics
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Cullin Proteins / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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F-Box Proteins / genetics
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F-Box Proteins / metabolism
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MAP Kinase Signaling System / drug effects*
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Mitogen-Activated Protein Kinases / genetics
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Mitogen-Activated Protein Kinases / metabolism
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Molecular Sequence Data
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Mutation
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Pheromones / pharmacology*
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Phosphorylation / drug effects
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Protein Binding / drug effects
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SKP Cullin F-Box Protein Ligases / deficiency
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SKP Cullin F-Box Protein Ligases / genetics
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SKP Cullin F-Box Protein Ligases / metabolism
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Saccharomyces cerevisiae / drug effects*
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism*
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism*
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Substrate Specificity
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Threonine / genetics
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Threonine / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Ubiquitin / genetics
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Ubiquitin / metabolism
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Ubiquitin-Protein Ligase Complexes / genetics
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Ubiquitin-Protein Ligase Complexes / metabolism
Substances
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Cdc53 protein, S cerevisiae
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Cell Cycle Proteins
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Cullin Proteins
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DNA-Binding Proteins
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Dia2 protein, S cerevisiae
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F-Box Proteins
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Pheromones
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Saccharomyces cerevisiae Proteins
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TEC1 protein, S cerevisiae
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Transcription Factors
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Ubiquitin
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Threonine
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Ubiquitin-Protein Ligase Complexes
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Anaphase-Promoting Complex-Cyclosome
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SKP Cullin F-Box Protein Ligases
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FUS3 protein, S cerevisiae
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Mitogen-Activated Protein Kinases