Kel1 is a phosphorylation-regulated noise suppressor of the pheromone signaling pathway

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Garcia, Ignacio, Orellana-Munoz, Sara, Ramos-Alonso, Lucia, Andersen, Aram N, Zimmermann, Christine, Eriksson, Jens, Boe, Stig Ove, Kaferle, Petra, Papamichos-Chronakis, Manolis ORCID: 0000-0002-4144-2070, Chymkowitch, Pierre et al (show 1 more authors) and Enserink, Jorrit M (2021) Kel1 is a phosphorylation-regulated noise suppressor of the pheromone signaling pathway. CELL REPORTS, 37 (13). 110186-.

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Official URL: http://dx.doi.org/10.1016/j.celrep.2021.110186

Abstract

Mechanisms have evolved that allow cells to detect signals and generate an appropriate response. The accuracy of these responses relies on the ability of cells to discriminate between signal and noise. How cells filter noise in signaling pathways is not well understood. Here, we analyze noise suppression in the yeast pheromone signaling pathway and show that the poorly characterized protein Kel1 serves as a major noise suppressor and prevents cell death. At the molecular level, Kel1 prevents spontaneous activation of the pheromone response by inhibiting membrane recruitment of Ste5 and Far1. Only a hypophosphorylated form of Kel1 suppresses signaling, reduces noise, and prevents pheromone-associated cell death, and our data indicate that the MAPK Fus3 contributes to Kel1 phosphorylation. Taken together, Kel1 serves as a phospho-regulated suppressor of the pheromone pathway to reduce noise, inhibit spontaneous activation of the pathway, regulate mating efficiency, and prevent pheromone-associated cell death.

Item Type:	Article
Uncontrolled Keywords:	Saccharomyces cerevisiae, Mitogen-Activated Protein Kinases, Adaptor Proteins, Signal Transducing, Saccharomyces cerevisiae Proteins, Pheromones, Noise, Signal Transduction, Phosphorylation, Cyclin-Dependent Kinase Inhibitor Proteins
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	25 May 2022 09:09
Last Modified:	18 Jan 2023 21:01
DOI:	10.1016/j.celrep.2021.110186
Open Access URL:	https://doi.org/10.1016/j.celrep.2021.110186
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3155459