The Ste5p scaffold.
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.
Elion
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Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA. elaine_elion@hms.harvard.edu
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D016764:Cell Polarity; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008954:Models, Biological; D020836:Protein Structure, Quaternary; D029701:Saccharomyces cerevisiae Proteins; D015003:Yeasts / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D005656:Fungal Proteins; C080321:STE5 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D020962:Heterotrimeric GTP-Binding Proteins