The HST7 gene of Candida albicans encodes a protein with structural similarity to MAP kinase kinases. Expression of this gene in Saccharomyces cerevisiae complements disruption of the Ste7 MAP kinase kinase required for both mating in haploid cells and pseudohyphal growth in diploids. However, Hst7 expression does not complement loss of either the Pbs2 (Hog4) MAP kinase kinase required for response to high osmolarity, or loss of the Mkk1 and Mkk2 MAP kinase kinases required for proper cell wall biosynthesis. Intriguingly, HST7 acts as a hyperactive allele of STE7; expression of Hst7 activates the mating pathway even in the absence of upstream signaling components including the Ste7 regulator Ste11, elevates the basal level of the pheromone-inducible FUS1 gene, and amplifies the pseudohyphal growth response in diploid cells. Thus Hst7 appears to be at least partially independent of upstream activators or regulators, but selective in its activity on downstream target MAP kinases. Creation of Hst7/Ste7 hybrid proteins revealed that the C-terminal two-thirds of Hst7, which contains the protein kinase domain, is sufficient to confer this partial independence of upstream activators.
Bibliographical noteAcknowledgments We thank Brian Stevenson, Charlie Boone, George Sprague, Mark Payton, Mike Gustin, Beverly Errede, Gerry Fink and Kunihiro Matsumoto for plasmids and yeast strains. Many thanks to Beatrice Magee for the Candida mapping data, and Beverly Errede for unpublished data. We also thank Rolf Swoboda,
Julia White and Chris Paddon for advice, plasmids and yeast strains, and Adrian Hobden for his support. This work was supported by a collaborative agreement with Glaxo and Glaxo (Canada) Ltd. PJFF was supported by a Glaxo Group Research Studentship (S/502). This is NRCC publication number 38553.
- Candida albicans
- MAP kinase kinase
- Saccharomyces cerevisiae