Graded mode of transcriptional induction in yeast pheromone signalling revealed by single-cell analysis

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.