Control of Membrane Localization
The protein Ste5 plays a critical role in pheromone signaling. It is calleda "scaffold" protein for its ability to bind multiple kinases of the MAP kinase cascade andpromote their interaction. An important early step in pheromone response is therecruitment of Ste5 to the plasma membrane, which is mediated by the G protein beta-gamma dimer (Gβγ).Yet, this interaction is not sufficient. Instead, Ste5 recruitment requires a synergistic effectof two weak interactions: a protein-protein interaction and a protein-membraneinteraction. The membrane interaction is mediated by a sequence called the PM domain,which is a putative amphipathic alpha helix that binds acidic phospholipid membranes invivo and in vitro. We also found similar domains, and a similar synergistic localization, inother signaling proteins.Currently, we continue to explore new sequences, and investigate the potential benefitsof synergistic binding; possibilities include greater evolutionary plasticity, increasedspatial and temporal dynamics, and expanded opportunities for signal integration.
