An emerging theme of mitogen-activated protein kinase (MAPK) cascades is that they form molecular assemblies within cells; the spatial organization of which is provided by scaffold proteins. Yeast Ste5p was the first MAPK cascade scaffold to be described. Early work demonstrated that Ste5p selectively tethers the MAPKKK, MAPKK and MAPK of the yeast mating pathway and is essential for efficient activation of the MAPK by the pheromone stimulus. Recent work indicates that Ste5p is not a passive scaffold but plays a direct role in the activation of the MAPKKK by a heterotrimeric G protein and PAK-type kinase. This activation event requires the formation of an active Ste5p oligomer and proper recruitment of Ste5p to a Gbetagamma dimer at the submembrane of the cell cortex, which suggests that Ste5p forms a stable Ste5p signalosome linked to a G protein. Additional studies underscore the importance of regulated localization of Ste5p to the plasma membrane and have revealed nuclear shuttling as a regulatory device that controls the access of Ste5p to the plasma membrane. A model that links Ste5p oligomerization with stable membrane recruitment is presented. In this model, pathway activation is coordinated with the conversion of a less active closed form of Ste5 containing a protected RING-H2 domain into an active Ste5p dimer that can bind to Gbetagamma and form a multimeric scaffold lattice upon which the MAPK cascade can assemble.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Annotation Extension||Reference|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Assay||Construct||Conditions||Strain Background||Reference|