Journal Article

Ste5 Scaffold Allosterically Modulates Signaling Output of the Yeast Mating Pathway

Remenyi, Attila, Falick, Arnold M, Good, Matthew C, Bashor, Caleb J, Lim, Wendell A, Bhattacharyya, Roby P

2006

Overview

Scaffold proteins organize signaling proteins into pathways and are often viewed as passive assembly platforms. We found that the Ste5 scaffold has a more active role in the yeast mating pathway: A fragment of Ste5 allosterically activated autophosphorylation of the mitogen-activated protein kinase Fus3. The resulting form of Fus3 is partially active--it is phosphorylated on only one of two key residues in the activation loop. Unexpectedly, at a systems level, autoactivated Fus3 appears to have a negative regulatory role, promoting Ste5 phosphorylation and a decrease in pathway transcriptional output. Thus, scaffolds not only direct basic pathway connectivity but can precisely tune quantitative pathway input-output properties.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Adaptor Proteins, Signal Transducing - chemistry / Adaptor Proteins, Signal Transducing - genetics / Adaptor Proteins, Signal Transducing - metabolism / Alleles / Allosteric Regulation / Amino Acid Motifs / Amino acids / autophosphorylation / Binding Sites / Biological and medical sciences / Crystallography, X-Ray / Cytometry / Down-Regulation / Drug interactions / Enzyme Activation / Enzymes / Fundamental and applied biological sciences. Psychology / gene expression / Growth, nutrition, metabolism, transports, enzymes. Molecular biology / MAP Kinase Signaling System / Microbiology / mitogen-activated protein kinase / Mitogen-Activated Protein Kinases - chemistry / Mitogen-Activated Protein Kinases - metabolism / Models, Biological / Models, Molecular / Mutation / Mycology / Pheromones / Pheromones - physiology / Phosphorylation / Protein Binding / Protein Conformation / protein phosphorylation / Protein Structure, Secondary / Protein Structure, Tertiary / protein-protein interactions / Proteins / Research Article / Saccharomyces cerevisiae / Saccharomyces cerevisiae - genetics / Saccharomyces cerevisiae - metabolism / Saccharomyces cerevisiae Proteins - chemistry / Saccharomyces cerevisiae Proteins - genetics / Saccharomyces cerevisiae Proteins - metabolism / Scaffolds / sexual reproduction / Signal transduction / transcription (genetics) / Transcription, Genetic / Yeast / Yeasts