We are upgrading the repository! A content freeze is in effect until December 6, 2024. New submissions or changes to existing items will not be allowed during this period. All content already published will remain publicly available for searching and downloading. Updates will be posted in the Website Upgrade 2024 FAQ in the sidebar Help menu. Reach out to escholarship@umassmed.edu with any questions.
Membrane localization of scaffold proteins promotes graded signaling in the yeast MAP kinase cascade
Name:
Publisher version
View Source
Access full-text PDFOpen Access
View Source
Check access options
Check access options
UMass Chan Affiliations
Department of Molecular Genetics and MicrobiologyDocument Type
Journal ArticlePublication Date
2008-08-30Keywords
Adaptor Proteins, Signal TransducingCell Membrane
Genes, Fungal
*MAP Kinase Signaling System
Mutation
Pheromones
Receptor Cross-Talk
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
BACKGROUND: Signaling through mitogen-activated protein kinase (MAPK) cascade pathways can show various input-output behaviors, including either switch-like or graded responses to increasing levels of stimulus. Prior studies suggest that switch-like behavior is promoted by positive feedback loops and nonprocessive phosphorylation reactions, but it is unclear whether graded signaling is a default behavior or whether it must be enforced by separate mechanisms. It has been hypothesized that scaffold proteins promote graded behavior. RESULTS: Here, we experimentally probe the determinants of graded signaling in the yeast mating MAPK pathway. We find that graded behavior is robust in that it resists perturbation by loss of several negative-feedback regulators. However, the pathway becomes switch-like when activated by a crosstalk stimulus that bypasses multiple upstream components. To dissect the contributing factors, we developed a method for gradually varying the signal input at different pathway steps in vivo. Input at the beginning of the kinase cascade produced a sharp, threshold-like response. Surprisingly, the scaffold protein Ste5 increased this threshold behavior when limited to the cytosol. However, signaling remained graded whenever Ste5 was allowed to function at the plasma membrane. CONCLUSIONS: The results suggest that the MAPK cascade module is inherently ultrasensitive but is converted to a graded system by the pathway-specific activation mechanism. Scaffold-mediated assembly of signaling complexes at the plasma membrane allows faithful propagation of weak signals, which consequently reduces pathway ultrasensitivity. These properties help shape the input-output properties of the system to fit the physiological context.Source
Curr Biol. 2008 Aug 26;18(16):1184-91. Link to article on publisher's site
DOI
10.1016/j.cub.2008.07.050Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39240PubMed ID
18722124Related Resources
ae974a485f413a2113503eed53cd6c53
10.1016/j.cub.2008.07.050