title: Graded mode of transcriptional induction in yeast pheromone signalling revealed by single-cell analysis.
abstract: Signalling pathways typically convert a graded, analogue signal into a binary cellular output. In the several eukaryotic systems that have been investigated to date, including MAP kinase cascade activation in Xenopus oocytes, analogue-to-digital conversion occurs at points in the pathway between receptor activation and the effector mechanism. We used flow cytometry combined with an intracellular fluorescent reporter to examine the characteristics of the yeast pheromone-response pathway. Surprisingly, pheromone response in yeast, which relies on the MAP kinase cascade, behaved in a fundamentally graded manner. Expression of certain exogenous dominant inhibitors of the pathway converted the response to graded-or-none behaviour. These results have implications for the dissection of biological response mechanisms in cells and illustrate how signalling pathways, even homologous ones, may have strikingly different signal propagation/amplification characteristics.
authors.affiliation: Arcaris Inc., 615 Arapeen Drive, Suite 300, Salt Lake City, UT 84108, USA. poritz@arcaris.com
authors.forename: M A
authors.initials: MA
authors.lastname: Poritz
authors.forename: S
authors.initials: S
authors.lastname: Malmstrom
authors.forename: M K
authors.initials: MK
authors.lastname: Kim
authors.forename: P J
authors.initials: PJ
authors.lastname: Rossmeissl
authors.forename: A
authors.initials: A
authors.lastname: Kamb
mesh_terms: D005434:Flow Cytometry; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins; D010446:Peptide Fragments / Q000494:pharmacology; D010675:Pheromones / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C490024:FUS1 protein, S cerevisiae; D005656:Fungal Proteins; D008164:Luminescent Proteins; D008565:Membrane Proteins; D010446:Peptide Fragments; D010675:Pheromones; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins