Signal Propagation and Regulation in the Mating Pheromone Response Pathway of the Yeast Saccharomyces cerevisiae

Bardwell, Lee; Cook, Jeanette Gowen; Inouye, Carla; Thorner, Jeremy

doi:10.1006/dbio.1994.1323

Cited by 156 publications

(113 citation statements)

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“…As this is not intended to be a comprehensive review, I will not attempt to cite a primary reference source for each fact I mention. This information is available in the many excellent reviews of aspects of this pathway that have been published over the last decade [9,32,33,37,56,60,85,115].…”

Section: Introductionmentioning

confidence: 99%

A walk-through of the yeast mating pheromone response pathway

2004

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Section: Introductionmentioning

confidence: 99%

A walk-through of the yeast mating pheromone response pathway

2004

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“…for pheromone response is perhaps the best understood signal transduction pathway known in any eukaryotic organism (Bardwell et al 1994b), and components of this pathway are evolutionarily conserved in metazoans (Dhanasekaran et al 1995). The mating pheromones bind to cell type-specific, G protein-coupled receptors.…”

mentioning

confidence: 99%

Two novel targets of the MAP kinase Kss1 are negative regulators of invasive growth in the yeast Saccharomyces cerevisiae.

Cook¹,

Bardwell²,

Kron³

et al. 1996

Genes Dev.

210

217

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Haploid cells of budding yeast Saccharomyces cerevisiae respond to mating pheromones by inducing genes required for conjugation, arresting cell cycle progression, and undergoing morphological changes. The same cells respond to nutrient deprivation by altering budding pattern and inducing genes required for invasive growth. Both developmental alternatives to vegetative proliferation require the MAP kinase Kssl and the transcriptional transactivator Stel2. Using a two-hybrid screen for gene products that interact with Kssl, two homologous and previously uncharacterized loci (DIG1 and DIG2, for down-regulator of invasive growth) were identified. DIG2 is pheromone-inducible, whereas DIG1 is constitutively expressed. Digl~ colocalizes with Kssl in the nucleus, coimmunoprecipitates with Kssl from cell extracts in a pheromone-independent manner, and is phosphorylated by Kssl in immune complexes in a pheromone-stimulated manner. Kssl binds specifically to a GST-Digl fusion in the absence of any other yeast protein. Using the two-hybrid method, both Digl and Dig2 also interact with the other MAP kinase of the pheromone response pathway, Fus3.However, neither digl or dig2 single mutants, nor a digl dig2 double mutant, have a discernible effect on mating. In contrast, digl dig2 cells constitutively invade agar medium, whereas a digl dig2 stel2 triple mutant does not, indicating that Digl and Dig2 share a role in negatively regulating the invasive growth pathway. High-level expression of Digl suppresses invasive growth and also causes cells to appear more resistant to pheromone-imposed cell cycle arrest. Stel2 also binds specifically to GST-Digl in the absence of any other yeast protein. Collectively, these findings indicate that Digl, and most likely Dig2, are physiological substrates of Kssl and suggest that they regulate Stel2 function by direct protein-protein interaction.

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“…In S. cerevisiae, the mating pheromones (a-and α-factors) secreted from MATa and MATα haploid cells, respectively, also bind to heterotrimeric G protein-coupled cell surface receptors of opposite mating type cells and induce the mating response, which results in production of diploids (Bardwell et al, 1994;Blumer and Thorner, 1991;Marsh et al, 1991;Sprague and Thorner, 1992). Genetic and molecular studies on the G protein-receptor signaling in S. cerevisiae have shown that the components of this signaling pathway are structurally and functionally similar to those in higher eukaryotic cells.…”

mentioning

confidence: 99%

Ca+2 Signal is Generated Only Once in the Mating Pheromone Response Pathway in Saccharomyces cerevisiae.

Nakajima‐Shimada

Sakaguchi

Tsuji

et al. 2000

Cell Struct. Funct.

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ABSTRACT. The mating pheromone, α-factor, of the yeast Saccharomyces cerevisiae binds to the heterotrimeric G protein-coupled cell surface receptor of MATa cells and induces cellular responses necessary for mating. In higher eukaryotic cells, many hormones and growth factors rapidly mobilize a second messenger, Ca 2+ , by means of receptor-G protein signaling. Although striking similarities between the mechanisms of the receptor-G protein signaling in yeast and higher eukaryotes have long been known, it is still uncertain whether the pheromone rapidly mobilizes Ca 2+ necessary for early events of the pheromone response. Here we reexamine this problem using sensitive methods for detecting Ca 2+ fluxes and mobilization, and find no evidence that there is rapid Ca 2+ influx leading to a rapid increase in the cytosolic free Ca 2+ concentration. In addition, the yeast PLC1 deletion mutant lacking phosphoinositide-specific phospholipase C, a key enzyme for generating Ca 2+ signals in higher eukaryotic cells, responds normally to the pheromone. These findings suggest that the receptor-G protein signaling does not utilize Ca 2+ as a second messenger in the early stage of the pheromone response pathway. Since the receptor-G protein signaling does stimulate Ca 2+ influx after early events have finished and this stimulation is essential for late events in the pheromone response pathway {Iida et al., (1990) J. Biol. Chem., 265: 13391-13399} Ca 2+ may be used only once in the signal transduction pathway in unicellular eukaryotes such as yeast.

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Signal Propagation and Regulation in the Mating Pheromone Response Pathway of the Yeast Saccharomyces cerevisiae

Cited by 156 publications

References 0 publications

A walk-through of the yeast mating pheromone response pathway

A walk-through of the yeast mating pheromone response pathway

Two novel targets of the MAP kinase Kss1 are negative regulators of invasive growth in the yeast Saccharomyces cerevisiae.

Ca+2 Signal is Generated Only Once in the Mating Pheromone Response Pathway in Saccharomyces cerevisiae.

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