Pheromone-dependent ubiquitination of the mitogen-activated protein kinase kinase Ste7.
Many cell signaling pathways are regulated by phosphorylation, ubiquitination, and degradation of constituent proteins. As with phosphorylation, protein ubiquitination can be reversed, through the action of ubiquitin-specific processing proteases (UBPs). Here we have analyzed 15 UBP disruption mutants in the yeast Saccharomyces cerevisiae and identified one (ubp3 Delta) that acts specifically in the pheromone response pathway. Upon pheromone stimulation, ubp3 Delta mutants accumulate unconjugated polyubiquitin chains as well as polyubiquitinated forms of the mitogen-activated protein kinase kinase Ste7. The ubp3 Delta mutants exhibit a potentiated response to pheromone, as measured by in vivo MAP kinase activity, transcriptional induction, and cell cycle arrest. Signaling is likewise enhanced upon direct activation of Ste4 (G protein beta subunit) and Ste11 (Ste7 kinase) but not the downstream transcription factor Ste12. These findings reveal a mechanism by which pheromone-triggered ubiquitination of Ste7 can modulate the pheromone response in vivo.
Wang
Yuqi
Y
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599-2852, USA.
Dohlman
Henrik G
HG
D002455:Cell Division; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism; D017353:Gene Deletion; D007700:Kinetics; D000072235:Mating Factor; D020929:Mitogen-Activated Protein Kinase Kinases; D016296:Mutagenesis; D010455:Peptides / Q000235:genetics / Q000502:physiology*; D010675:Pheromones / Q000502:physiology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism*
D005656:Fungal Proteins; D010455:Peptides; D010675:Pheromones; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D000072235:Mating Factor; D011494:Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C119844:STE7 protein, S cerevisiae; D010450:Endopeptidases; C101111:UBP3 protein, S cerevisiae