Functional binding between Gβ and the LIM domain of Ste5 is required to activate the MEKK Ste11

Yuanyi Feng, Lin Ye Song, Eleanor Kincaid, Sanjoy K. Mahanty, Elaine A. Elion*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

89 Scopus citations


Background: In the budding yeast Saccharomyces cerevisiae, the pheromones that induce haploid cells of opposite cell types to mate activate the Gβ and Gγ subunits of a heterotrimeric G protein. These subunits signal through the PAK kinase Ste20 to activate a mitogen-activated protein (MAP) kinase cascade comprising the MEKK Ste11, the MEK Ste7 and two MAP kinases, Fus3 and Kss1. The pathway requires Ste5, a scaffold protein that tethers the MAP kinase cascade enzymes into a high molecular weight complex. Ste5 is thought to associate with Gβ in a pheromone-independent manner, but it is not known if this interaction affects signaling. Results: A ste5C180A mutant - which expresses Ste5 disrupted in the LIM domain, a putative metal-binding motif that has been proposed to be essential for Ste5 oligomerization -could not transmit the pheromone signal from Gβ through Ste20 to Ste11. The Ste5C180A protein was impaired in binding Gβ, although it could oligomerize, bind Ste11, Ste7 and Fus3, facilitate the basal activation of Ste11, and relay the Ste11 signal to MAP kinases. Ste5 bound to Gβ in a pheromone-dependent manner and preferentially associated with a phosphorylated form of Gβ in wild-type and ste20Δ, but not in ste5C180A, strains. Conclusions: Pheromone induces binding of Gβ to Ste5 through its LIM domain. This binding is essential for activation of Ste11 and is distinct from the ability of Ste5 to oligomerize or to serve as a scaffold and relay the signal from Ste11 to the MAP kinases. Pheromone also induces Ste5-dependent phosphorylation of Gβ.

Original languageEnglish (US)
Pages (from-to)267-282
Number of pages16
JournalCurrent Biology
Issue number5
StatePublished - Feb 26 1998

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)


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