MAPK specificity in the yeast pheromone response independent of transcriptional activation

• Published in: Current biology Vol. 11; no. 16; pp. 1266 - 1271
• Main Authors: Breitkreutz, Ashton, Boucher, Lorrie, Tyers, Mike
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 21-08-2001
• Subjects: Cell Cycle Proteins; Cyclin-Dependent Kinase Inhibitor Proteins; Enzyme Inhibitors - metabolism; Far1 protein; Fungal Proteins - genetics; Fungal Proteins - metabolism; Fus3 protein; Kss1 protein; MAP Kinase Signaling System - physiology; Mitogen-Activated Protein Kinases - genetics; Mitogen-Activated Protein Kinases - metabolism; Models, Biological; Oligonucleotide Array Sequence Analysis; Peptides - metabolism; Pheromones - pharmacology; Recombinant Proteins - metabolism; Repressor Proteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - physiology; Saccharomyces cerevisiae Proteins; Statistics as Topic; Ste12 protein; Ste5 protein; Transcriptional Activation
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/S0960-9822(01)00370-0

The mechanisms whereby different external cues stimulate the same mitogen-activated protein kinase (MAPK) cascade, yet trigger an appropriately distinct biological response, epitomize the conundrum of specificity in cell signaling. In yeast, shared upstream components of the mating pheromone and filamentous growth pathways activate two related MAPKs, Fus3 and Kss1, which in turn regulate programs of gene expression via the transcription factor Ste12 [1]. As fus3, but not kss1, strains are impaired for mating, Fus3 exhibits specificity for the pheromone response. To account for this specificity, it has been suggested that Fus3 physically occludes Kss1 from pheromone-activated signaling complexes, which are formed on the scaffold protein Ste5 [2]. However, we find that genome-wide expression profiles of pheromone-treated wild-type, fus3, and kss1 deletion strains are highly correlated for all induced genes and, further, that two catalytically inactive versions of Fus3 fail to abrogate the pheromone-induced transcriptional response. Consistently, Fus3 and Kss1 kinase activity is induced to an equivalent extent in pheromone-treated cells. In contrast, both in vivo and in an in vitro-reconstituted MAPK system, Fus3, but not Kss1, exhibits strong substrate selectivity toward Far1, a bifunctional protein required for polarization and G1 arrest [3, 4]. This effect accounts for the failure to repress G1-S specific transcription in fus3 strains and, in part, explains the mating defect of such strains. MAPK specificity in the pheromone response evidently occurs primarily at the substrate level, as opposed to specific kinase activation by dedicated signaling complexes.