How to Select a Mate: Kel1 is a Phosphorylation-Regulated Suppressor of the Pheromone Signaling Pathway

2021 ◽  
Author(s):  
Ignacio Garcia ◽  
Sara Munoz ◽  
Pierre Chymkowitch ◽  
Manolis Papamichos-Chronakis ◽  
Aram Nikolai Andersen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Pheromone Signaling

scholarly journals Mot3, a Zn Finger Transcription Factor That Modulates Gene Expression and Attenuates Mating Pheromone Signaling in Saccharomyces cerevisiae

Genetics ◽  
1998 ◽  
Vol 149 (2) ◽  
pp. 879-892 ◽  
Author(s):  
Anatoly V Grishin ◽  
Michael Rothenberg ◽  
Maureen A Downs ◽  
Kendall J Blumer
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Signaling Pathway ◽  
G Protein ◽  
Binding Sites ◽  
Dependent Manner ◽  
Pheromone Response ◽  
Mating Pheromone ◽  
Pheromone Signaling ◽  
Yeast Genes

Abstract In the yeast Saccharomyces cerevisiae, mating pheromone response is initiated by activation of a G protein- and mitogen-activated protein (MAP) kinase-dependent signaling pathway and attenuated by several mechanisms that promote adaptation or desensitization. To identify genes whose products negatively regulate pheromone signaling, we screened for mutations that suppress the hyperadaptive phenotype of wild-type cells overexpressing signaling-defective G protein β subunits. This identified recessive mutations in MOT3, which encodes a nuclear protein with two Cys2-His2 Zn fingers. MOT3 was found to be a dosage-dependent inhibitor of pheromone response and pheromone-induced gene expression and to require an intact signaling pathway to exert its effects. Several results suggested that Mot3 attenuates expression of pheromone-responsive genes by mechanisms distinct from those used by the negative transcriptional regulators Cdc36, Cdc39, and Mot2. First, a Mot3-lexA fusion functions as a transcriptional activator. Second, Mot3 is a dose-dependent activator of several genes unrelated to pheromone response, including CYC1, SUC2, and LEU2. Third, insertion of consensus Mot3 binding sites (C/A/T)AGG(T/C)A activates a promoter in a MOT3-dependent manner. These findings, and the fact that consensus binding sites are found in the 5′ flanking regions of many yeast genes, suggest that Mot3 is a globally acting transcriptional regulator. We hypothesize that Mot3 regulates expression of factors that attenuate signaling by the pheromone response pathway.

scholarly journals Quantitative Phosphoproteomics Applied to the Yeast Pheromone Signaling Pathway

2005 ◽  
Vol 4 (3) ◽  
pp. 310-327 ◽  
Author(s):  
Albrecht Gruhler ◽  
Jesper V. Olsen ◽  
Shabaz Mohammed ◽  
Peter Mortensen ◽  
Nils J. Færgeman ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Pheromone Signaling ◽  
Quantitative Phosphoproteomics

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

Cell Reports ◽  
2021 ◽  
Vol 37 (13) ◽  
pp. 110186
Author(s):  
Ignacio Garcia ◽  
Sara Orellana-Muñoz ◽  
Lucía Ramos-Alonso ◽  
Aram N. Andersen ◽  
Christine Zimmermann ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Pheromone Signaling

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

2021 ◽  
Author(s):  
Ignacio Garcia ◽  
Sara Munoz ◽  
Pierre Chymkowitch ◽  
Manolis Papamichos-Chronakis ◽  
Aram Nikolai Andersen ◽  
...  
Keyword(s):  
Cell Death ◽  
Signaling Pathway ◽  
Noise Suppression ◽  
Molecular Level ◽  
Time Resolved ◽  
Membrane Recruitment ◽  
Pheromone Signaling ◽  
Mating Efficiency ◽  
Spontaneous Activation ◽  
Filter Noise

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. We have analyzed noise suppression in the yeast pheromone signaling pathway. By combining synthetic genetic array screening, mass spectrometry and single-cell time-resolved microscopy, we discovered that the poorly characterized protein Kel1 serves as a major noise suppressor of the pathway. At the molecular level, Kel1 suppresses spontaneous activation of the pheromone response by inhibiting membrane recruitment of Ste5 and Far1. Kel1 is regulated by phosphorylation, and only the hypophosphorylated form of Kel1 suppresses signaling, reduces noise and prevents pheromone-associated cell death. Our data indicate that in response to pheromone the MAPKs Fus3 and Kss1 phosphorylate Kel1 to relieve inhibition of the pheromone pathway. 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 to prevent pheromone-associated cell death.

scholarly journals Feedback Phosphorylation of the Yeast a-Factor Receptor Requires Activation of the Downstream Signaling Pathway from G Protein through Mitogen-Activated Protein Kinase

2000 ◽  
Vol 20 (2) ◽  
pp. 563-574 ◽  
Author(s):  
Ying Feng ◽  
Nicholas G. Davis
Keyword(s):  
Plasma Membrane ◽  
Protein Kinase ◽  
Signaling Pathway ◽  
G Protein ◽  
Signal Transduction Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Striking Difference ◽  
Signaling Mechanism ◽  
Pheromone Signaling ◽  
Mitogen Activated Protein

ABSTRACT The two yeast pheromone receptors, the a and α-factor receptors, share many functional similarities: both G protein-coupled receptors couple to the same downstream signal transduction pathway, and both receptors undergo feedback regulation involving increased phosphorylation on their C-terminal domains in response to ligand challenge. The present work, which focuses on the signaling mechanism controlling this feedback phosphorylation, indicates one striking difference. While the α-factor-induced phosphorylation of the α-factor receptor does not require activation of the downstream G protein-directed signaling pathway (B. Zanolari, S. Raths, B. Singer-Kruger, and H. Riezman, Cell 71:755–763, 1992), the a-factor-induced phosphorylation of the a-factor receptor (Ste3p) clearly does. Induced Ste3p phosphorylation was blocked in cells with disruptions of various components of the pheromone response pathway, indicating a requirement of pathway components extending from the G protein down through the mitogen-activated protein kinase (MAPK). Furthermore, Ste3p phosphorylation can be induced in the absence of the a-factor ligand when the signaling pathway is artificially activated, indicating that the liganded receptor is not required as a substrate for induced phosphorylation. While the activation of signaling is critical for the feedback phosphorylation of Ste3p, pheromone-induced gene transcription, one of the major outcomes of pheromone signaling, appears not to be required. This conclusion is indicated by three results. First,ste12Δ cells differ from cells with disruptions of the upstream signaling elements (e.g., ste4Δ,ste20Δ, ste5Δ, ste11Δ,ste7Δ, or fus3Δ kss1Δ cells) in that they clearly retain some capacity for inducing Ste3p phosphorylation. Second, while activated alleles of STE11 andSTE12 induce a strong transcriptional response, they fail to induce a-factor receptor phosphorylation. Third, blocking of new pheromone-induced protein synthesis with cycloheximide fails to block phosphorylation. These findings are discussed within the context of a recently proposed model for pheromone signaling (P. M. Pryciak and F. A. Huntress, Genes Dev. 12:2684–2697, 1998): a key step of this model is the activation of the MAPK Fus3p through the Gβγ-dependent relocalization of the Ste5p-MAPK cascade to the plasma membrane. Ste3p phosphorylation may involve activated MAPK Fus3p feeding back upon plasma membrane targets.

Wnt signaling pathway regulates the differentiation of hepatic progenitor cells

2010 ◽  
Vol 34 (8) ◽  
pp. S41-S41
Author(s):  
Yang Bi ◽  
Yun He ◽  
Tingyu Li ◽  
Tao Feng ◽  
Tongchuan He
Keyword(s):  
Wnt Signaling ◽  
Progenitor Cells ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Hepatic Progenitor Cells

285: The Role of the NF-κB Signaling Pathway in the Pathogenesis of Interstitial Cystitis

2006 ◽  
Vol 175 (4S) ◽  
pp. 95-95
Author(s):  
Raymond R. Rackley ◽  
Mei Kuang ◽  
Ashwin A. Vaze ◽  
Joseph Abdelmalak ◽  
Sandip P. Vasavada ◽  
...  
Keyword(s):  
Interstitial Cystitis ◽  
Signaling Pathway

417: The Human Androgen Receptor Gene is a Primary Target of the WNT Signaling Pathway

2006 ◽  
Vol 175 (4S) ◽  
pp. 136-136
Author(s):  
Ralph Buttyan ◽  
Xuezhen Yang ◽  
Min-Wei Chen ◽  
Debra L. Bemis ◽  
Mitchell C. Benson ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Receptor Gene ◽  
Wnt Signaling Pathway ◽  
Androgen Receptor Gene ◽  
Primary Target ◽  
Human Androgen Receptor Gene ◽  
Human Androgen Receptor
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