A conserved protein interaction network involving the yeast MAP kinases Fus3 and Kss1

J Cell Biol. 2004 Jan 19;164(2):267-77. doi: 10.1083/jcb.200310021.


The Saccharomyces cerevisiae mitogen-activated protein kinases (MAPKs) Fus3 and Kss1 bind to multiple regulators and substrates. We show that mutations in a conserved docking site in these MAPKs (the CD/7m region) disrupt binding to an important subset of their binding partners, including the Ste7 MAPK kinase, the Ste5 adaptor/scaffold protein, and the Dig1 and Dig2 transcriptional repressors. Supporting the possibility that Ste5 and Ste7 bind to the same region of the MAPKs, they partially competed for Fus3 binding. In vivo, some of the MAPK mutants displayed reduced Ste7-dependent phosphorylation, and all of them exhibited multiple defects in mating and pheromone response. The Kss1 mutants were also defective in Kss1-imposed repression of Ste12. We conclude that MAPKs contain a structurally and functionally conserved docking site that mediates an overall positively acting network of interactions with cognate docking sites on their regulators and substrates. Key features of this interaction network appear to have been conserved from yeast to humans.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Binding Sites
  • Carrier Proteins / metabolism
  • Homeostasis
  • Mitogen-Activated Protein Kinase Kinases
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism*
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Kinases / metabolism
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Recombinant Proteins
  • STE5 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Protein Kinases
  • FUS3 protein, S cerevisiae
  • KSS1 protein, S cerevisiae
  • Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase Kinases
  • STE7 protein, S cerevisiae