Ste5

Ste5 is a scaffold protein in the pheromone response MAPK signaling pathway of the budding yeast Saccharomyces cerevisiae. By binding the core kinases of the cascade—MAPKKK Ste11, MAPKK Ste7, and MAPK Fus3—Ste5 assembles the signaling module and concentrates kinases and substrates at the site of signaling, enabling efficient transmission of the pheromone signal from the activated receptor to the transcriptional program that drives mating.

Ste5 contains regions that interact with each kinase and a membrane-targeting domain that relocates the complex to the plasma membrane in response to pheromone. This membrane localization concentrates signaling components, enhances pathway specificity, and helps prevent cross-talk with other MAPK pathways.

Genetic studies show that STE5 is essential for a robust pheromone response: mutants lacking Ste5 exhibit impaired Fus3 activation and mating projection formation, while overexpression can lead to constitutive signaling or growth defects. Regulation of Ste5 involves phosphorylation and changes in subcellular localization; pheromone signaling promotes its membrane association, and subsequent phosphorylation events contribute to disassembly and signal termination, producing a controlled, transient response.

Ste5 homologs and related scaffold proteins are found in other fungi, where they organize analogous MAPK cascades. As a central organizing element, Ste5 plays a key role in ensuring signaling fidelity, efficiency, and timing within the yeast mating pathway.