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Background  The protein kinase YakA is responsible for the growth arrest and induction of developmental processes that occur upon starvation of  Dictyostelium  cells.  yakA -   cells are aggregation deficient, have a faster cell cycle and are hypersensitive to oxidative and nitrosoative stress. With the aim of isolating members of the YakA pathway, suppressors of the death induced by nitrosoative stress in the  yakA -   cells were identified. One of the suppressor mutations occurred in  keaA , a gene identical to DG1106 and similar to Keap1 from mice and the Kelch protein from Drosophila, among others that contain Kelch domains.    Results  A mutation in  keaA  suppresses the hypersensitivity to oxidative and nitrosoative stresses but not the faster growth phenotype of  yakA -   cells. The growth profile of  keaA  deficient cells indicates that this gene is necessary for growth.  keaA  deficient cells are more resistant to nitrosoative and oxidative stress and  keaA  is necessary for the production and detection of cAMP. A morphological analysis of  keaA  deficient cells during multicellular development indicated that, although the mutant is not absolutely deficient in aggregation, cells do not efficiently participate in the process. Gene expression analysis using cDNA microarrays of wild-type and  keaA  deficient cells indicated a role for KeaA in the regulation of the cell cycle and pre-starvation responses.    Conclusions  KeaA is required for cAMP signaling following stress. Our studies indicate a role for kelch proteins in the signaling that regulates the cell cycle and development in response to changes in the environmental conditions.

KeaA, a Dictyostelium kelch-domain protein that regulates the response to stress and development