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The adaptor protein Ste50 directly modulates yeast MAPK signaling specificity through differential connections of its RA domain

Discriminating among diverse environmental stimuli is critical for organisms to ensure their proper development, homeostasis, and survival. Saccharomyces cerevisiae regulates mating, osmoregulation, and filamentous growth using three different MAPK signaling pathways that share common components and...

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Autores principales: Sharmeen, Nusrat, Sulea, Traian, Whiteway, Malcolm, Wu, Cunle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589780/
https://www.ncbi.nlm.nih.gov/pubmed/30650049
http://dx.doi.org/10.1091/mbc.E18-11-0708
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author Sharmeen, Nusrat
Sulea, Traian
Whiteway, Malcolm
Wu, Cunle
author_facet Sharmeen, Nusrat
Sulea, Traian
Whiteway, Malcolm
Wu, Cunle
author_sort Sharmeen, Nusrat
collection PubMed
description Discriminating among diverse environmental stimuli is critical for organisms to ensure their proper development, homeostasis, and survival. Saccharomyces cerevisiae regulates mating, osmoregulation, and filamentous growth using three different MAPK signaling pathways that share common components and therefore must ensure specificity. The adaptor protein Ste50 activates Ste11p, the MAP3K of all three modules. Its Ras association (RA) domain acts in both hyperosmolar and filamentous growth pathways, but its connection to the mating pathway is unknown. Genetically probing the domain, we found mutants that specifically disrupted mating or HOG-signaling pathways or both. Structurally these residues clustered on the RA domain, forming distinct surfaces with a propensity for protein–protein interactions. GFP fusions of wild-type (WT) and mutant Ste50p show that WT is localized to the shmoo structure and accumulates at the growing shmoo tip. The specifically pheromone response–defective mutants are severely impaired in shmoo formation and fail to localize ste50p, suggesting a failure of association and function of Ste50 mutants in the pheromone-signaling complex. Our results suggest that yeast cells can use differential protein interactions with the Ste50p RA domain to provide specificity of signaling during MAPK pathway activation.
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spelling pubmed-65897802019-07-15 The adaptor protein Ste50 directly modulates yeast MAPK signaling specificity through differential connections of its RA domain Sharmeen, Nusrat Sulea, Traian Whiteway, Malcolm Wu, Cunle Mol Biol Cell Articles Discriminating among diverse environmental stimuli is critical for organisms to ensure their proper development, homeostasis, and survival. Saccharomyces cerevisiae regulates mating, osmoregulation, and filamentous growth using three different MAPK signaling pathways that share common components and therefore must ensure specificity. The adaptor protein Ste50 activates Ste11p, the MAP3K of all three modules. Its Ras association (RA) domain acts in both hyperosmolar and filamentous growth pathways, but its connection to the mating pathway is unknown. Genetically probing the domain, we found mutants that specifically disrupted mating or HOG-signaling pathways or both. Structurally these residues clustered on the RA domain, forming distinct surfaces with a propensity for protein–protein interactions. GFP fusions of wild-type (WT) and mutant Ste50p show that WT is localized to the shmoo structure and accumulates at the growing shmoo tip. The specifically pheromone response–defective mutants are severely impaired in shmoo formation and fail to localize ste50p, suggesting a failure of association and function of Ste50 mutants in the pheromone-signaling complex. Our results suggest that yeast cells can use differential protein interactions with the Ste50p RA domain to provide specificity of signaling during MAPK pathway activation. The American Society for Cell Biology 2019-03-15 /pmc/articles/PMC6589780/ /pubmed/30650049 http://dx.doi.org/10.1091/mbc.E18-11-0708 Text en © 2019 Sharmeen et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
spellingShingle Articles
Sharmeen, Nusrat
Sulea, Traian
Whiteway, Malcolm
Wu, Cunle
The adaptor protein Ste50 directly modulates yeast MAPK signaling specificity through differential connections of its RA domain
title The adaptor protein Ste50 directly modulates yeast MAPK signaling specificity through differential connections of its RA domain
title_full The adaptor protein Ste50 directly modulates yeast MAPK signaling specificity through differential connections of its RA domain
title_fullStr The adaptor protein Ste50 directly modulates yeast MAPK signaling specificity through differential connections of its RA domain
title_full_unstemmed The adaptor protein Ste50 directly modulates yeast MAPK signaling specificity through differential connections of its RA domain
title_short The adaptor protein Ste50 directly modulates yeast MAPK signaling specificity through differential connections of its RA domain
title_sort adaptor protein ste50 directly modulates yeast mapk signaling specificity through differential connections of its ra domain
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589780/
https://www.ncbi.nlm.nih.gov/pubmed/30650049
http://dx.doi.org/10.1091/mbc.E18-11-0708
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