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

Signalling pathways typically convert a graded, analogue signal into a bina ry cellular output. In the several eukaryotic systems that have been invest igated to date, including MAP kinase cascade activation in Xenopus oocytes, analogue-to-digital conversion occurs at points in the pathway between rec eptor activation and the effector mechanism. We used flow cytometry combine d 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 fundamentall y 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 c ells and illustrate how signalling pathways, even homologous ones, may have strikingly different signal propagation/amplification characteristics. Cop yright (C) 2001 John Wiley & Sons, Ltd.