MAPK signaling pathways are activated under various stress conditions and have been shown to be required for innate immunity in Caenorhabditis elegans and Arabidopsis thaliana (Asai et al. 2002). In C. elegans, mutants for
nsy-1, a MAPKKK, and
sek-1, a MAPKK, are highly susceptible to the pathogen, Pseudomonas aeruginosa PA14 (Kim et al. 2002). In addition, RNAi of the
p38 MAPK,
pmk-1, also led to enhanced susceptibility, but mutants for
unc-43, which activates NSY-1 to regulate AWC cell fate, are not susceptible (Sagasti et al. 2001). Arsenic has also been shown to activate
p38 MAPK signaling in mammalian cultured cells, and exposure of C. elegans to sodium arsenite induces
pmk-1. Furthermore,
sek-1 mutants are hypersensitive to sodium arsenite, and
nsy-1 mutants are partially susceptible to arsenite treatment. However,
unc-43 mutants are not sensitive to arsenite (Inoue et al. 2002). These findings mirror those of the susceptibility to PA14. In order to identify downstream targets of SEK-1 MAPK signaling which may be involved in the host response to PA14,
sek-1 worms were EMS mutanenized and screened for suppressors of the sodium arsenite susceptibility. Mutants identified from the screen were then tested for possible resistance to PA14 in order to determine the degree of overlap between the MAPK-mediated response to arsenic and to pathogen. Three mutants resistant to arsenic and PA14 have been identified thus far and further studies will include molecular identification and characterization of these mutants. Asai, T., et al. (2002). "MAP kinase signaling cascade in Arabidposis innate immunity." Nature 415(6875): 977-83. Inoue, H., et al. (2002). "C. elegans
p38 MAPK cascade mediates arsenical stress response." Worm Breeder's Gazette 17(2): 31; Kim, D. H., et al. (2002). "A Conserved
p38 MAP Kinase Pathway in Caenorhabditis elegans Innate Immunity." Science 297(5581): 623-626; Sagasti, A., et al. (2001). "The CaMKII UNC-43 activates the MAPKKK NSY-1 to execute a lateral signaling decision required for asymmetric olfactory neuron fates." Cell 105(2): 221-32.