Genetic interactions of the E3 ubiquitin ligase component FbxA with @entity1919 metabolism and a XXXX kinase signaling pathway during @entity4328 development.

@entity268 @entity4328 @entity1919 @entity3793
@entity4328 amoebae with an altered fbxA gene, which is thought to encode a component of an SCF E3 ubiquitin ligase, have defective regulation of cell type proportionality. In chimeras with wild-type cells, the mutant amoebae form mainly spores, leaving the construction of stalks to wild-type cells. To examine the role of fbxA and regulated proteolysis, we have recovered the promoter of fbxA and shown that it is expressed in a pattern resembling that of a prestalk-specific gene until late in development, when it is also expressed in developing spore cells. Because fbxA cells are developmentally deficient in pure culture, we were able to select suppressor mutations that promote sporulation of the original mutant. One suppressor mutation resides within the gene regA, which encodes a @entity1919 ( @entity268 ) phosphodiesterase linked to an activating response regulator domain. In another suppressor, there has been a disruption of dhkA, a gene encoding a two-component @entity3793 kinase known to influence @entity4328 development. RegA appears precociously and in greater amounts in the fbxA mutant than in the wild type, but in an fbxA/dhkA double mutant, RegA is restored to wild-type levels. Because the basis of regA suppression might involve alterations in @entity268 levels during development, the concentrations of @entity268 in all strains were determined. The levels of @entity268 are relatively constant during multicellular development in all strains except the dhkA mutant, in which it is reduced at least sixfold. The level of @entity268 in the double mutant dhkA/fbxA is relatively normal. The levels of @entity268 in the various mutants do not correlate with spore formation, as would be expected on the basis of our present understanding of the signaling pathway leading to the induction of spores. Altered amounts of RegA and @entity268 early in the development of the mutants suggest that both fbxA and dhkA genes act earlier than previously thought.
