| Title: | Kel1 is a phosphorylation-regulated noise suppressor of the pheromone signaling pathway |
| Author(s): | Garcia I; Orellana-Munoz S; Ramos-Alonso L; Andersen AN; Zimmermann C; Eriksson J; Boe SO; Kaferle P; Papamichos-Chronakis M; Chymkowitch P; Enserink JM; |
| Address: | "Department of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, 0379 Oslo, Norway; Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0318 Oslo, Norway. Section for Biochemistry and Molecular Biology, Faculty of Mathematics and Natural Sciences, University of Oslo, 0316 Oslo, Norway; Department of Microbiology, Oslo University Hospital, 0372 Oslo, Norway. Department of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, 0379 Oslo, Norway; Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0318 Oslo, Norway; Section for Biochemistry and Molecular Biology, Faculty of Mathematics and Natural Sciences, University of Oslo, 0316 Oslo, Norway. Institute for Virology, University Medical Center of the Johannes Gutenberg-University, 55131 Mainz, Germany. Department of Medical Biochemistry and Microbiology, Uppsala University, 752 37 Uppsala, Sweden. Department of Microbiology, Oslo University Hospital, 0372 Oslo, Norway. Institut Curie, PSL Research University, CNRS, UMR3664, Sorbonne Universities, Paris, France. Department of Molecular Physiology and Cell Signalling Institute of Systems, Molecular and Integrative Biology University of Liverpool, L69 7BE Liverpool, UK. Department of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, 0379 Oslo, Norway; Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0318 Oslo, Norway; Section for Biochemistry and Molecular Biology, Faculty of Mathematics and Natural Sciences, University of Oslo, 0316 Oslo, Norway. Electronic address: jorrit.enserink@rr-research.no" |
| DOI: | 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" |
| Keywords: | "Adaptor Proteins, Signal Transducing/genetics/*metabolism Cyclin-Dependent Kinase Inhibitor Proteins/genetics/metabolism Mitogen-Activated Protein Kinases/genetics/*metabolism *Noise Pheromones/*metabolism Phosphorylation Saccharomyces cerevisiae/genetics;" |
| Notes: | "MedlineGarcia, Ignacio Orellana-Munoz, Sara Ramos-Alonso, Lucia Andersen, Aram N Zimmermann, Christine Eriksson, Jens Boe, Stig Ove Kaferle, Petra Papamichos-Chronakis, Manolis Chymkowitch, Pierre Enserink, Jorrit M eng Research Support, Non-U.S. Gov't 2021/12/30 Cell Rep. 2021 Dec 28; 37(13):110186. doi: 10.1016/j.celrep.2021.110186" |
