• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


A membrane binding domain in the ste5 scaffold synergizes with gbetagamma binding to control localization and signaling in pheromone response.

Activation of mitogen-activated protein (MAP) kinase cascade signaling by yeast mating pheromones involves recruitment of the Ste5 scaffold protein to the plasma membrane by the receptor-activated Gbetagamma dimer. Here, we identify a putative amphipathic alpha-helical domain in Ste5 that binds directly to phospholipid membranes and is required for membrane recruitment by Gbetagamma. Thus, Ste5 signaling requires synergistic Ste5-Gbetagamma and Ste5-membrane interactions, with neither alone being sufficient. Remarkably, the Ste5 membrane binding domain is a dual-function motif that also mediates nuclear import. Separation-of-function mutations show that signaling requires the membrane-targeting activity of this domain, not its nuclear-targeting activity, and heterologous lipid binding domains can substitute for its function. This domain also contains imperfections that reduce membrane affinity, and their elimination results in constitutive signaling, explaining some previous hyperactive Ste5 mutants. Therefore, weak membrane affinity is advantageous, ensuring a normal level of signaling quiescence in the absence of stimulus and imposing a requirement for Gbetagamma binding.

Pubmed ID: 16209942


  • Winters MJ
  • Lamson RE
  • Nakanishi H
  • Neiman AM
  • Pryciak PM


Molecular cell

Publication Data

October 7, 2005

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM57769
  • Agency: NIGMS NIH HHS, Id: GM62184
  • Agency: NIGMS NIH HHS, Id: R01 GM057769
  • Agency: NIGMS NIH HHS, Id: R01 GM057769-06
  • Agency: NIGMS NIH HHS, Id: R01 GM057769-07
  • Agency: NIGMS NIH HHS, Id: R01 GM057769-08

Mesh Terms

  • Active Transport, Cell Nucleus
  • Adaptor Proteins, Signal Transducing
  • Cell Membrane
  • Heterotrimeric GTP-Binding Proteins
  • MAP Kinase Signaling System
  • Pheromones
  • Phospholipids
  • Protein Binding
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins