Dual role for membrane localization in yeast MAP kinase cascade activation and its contribution to signaling fidelity
Graduate School of Biomedical Sciences; Department of Molecular Genetics and Microbiology
Medical Subject Headings
Adaptor Proteins, Signal Transducing; Cell Membrane; Intracellular Membranes; MAP Kinase Signaling System; Models, Biological; Mutation; Plasmids; Protein Structure, Tertiary; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
Life Sciences | Medicine and Health Sciences
Distinct MAP kinase pathways in yeast share several signaling components , including the PAK Ste20 and the MAPKKK Ste11, yet signaling is specific. Mating pheromones trigger an initial step in which Ste20 activates Ste11 , and this requires plasma membrane recruitment of the MAP kinase cascade scaffold protein, Ste5 . Here, we demonstrate an additional role for Ste5 membrane localization. Once Ste11 is activated, signaling through the mating pathway remains minimal but is substantially amplified when Ste5 is recruited to the membrane either by the Gbetagamma dimer or by direct membrane targeting, even to internal membranes. Ste11 signaling is also amplified by Ste5 oligomerization and by a hyperactivating mutation in the Ste7 binding region of Ste5. We suggest a model in which membrane recruitment of Ste5 concentrates its binding partners and thereby amplifies signaling through the kinase cascade. We find similar behavior in the osmotically responsive HOG pathway. Remarkably, while both pheromone and hyperosmotic stimuli amplify signaling from constitutively active Ste11, the resulting signaling output remains pathway specific. These findings suggest a common mode of regulation in which pathway stimuli both initiate and amplify MAP kinase cascade signaling. The regulation of rate-limiting steps that lie after a branchpoint from shared components helps ensure signaling specificity.
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Citation: Curr Biol. 2006 Mar 21;16(6):618-23. Link to article on publisher's site
DOI of Published Version
Current biology : CB
Lamson, Rachel E.; Takahashi, Satoe; Winters, Matthew J.; and Pryciak, Peter M., "Dual role for membrane localization in yeast MAP kinase cascade activation and its contribution to signaling fidelity" (2006). GSBS Student Publications. 641.