| There are two primary immune systems in mammals, designated innate and adaptive. Innate immunity is the first-line host defense that serves to limit infection in the early stages. The innate immune response is highly conserved in evolution. For example, in Drosophila melanogaster, infections induce the secretion of a battery of anti-microbial peptides in the fat body, the functional equivalent of mammalian liver. Two pathways are relatively well-characterized in Drosophila innate immunity. The anti-fungal and Gram-positive bacterial innate immune response is controlled by the Toll signaling pathway, leading to the expression of several anti-microbial genes, including Drosomycin. The anti Gram-negative bacterial innate immune response requires several genes, including imd, ird-5 (a hIKKbeta homolog), key (a hIKKgamma homolog), and Relish (a p105 homolog). This pathway leads to the expression of many anti-microbial genes, including Diptericin .; This thesis work focuses on the Toll-mediated Drosophila anti-fungal and Gram-positive bacterial innate immune response with special emphases on the identification of the regulatory determinants required for the signal-dependent phosphorylation of Cactus, the identification of the F-box protein required for Drosomycin induction, and the investigation of the possibility of DmIKKs and Pelle as the Cactus kinase(s).; I show that Cactus serine residues 74 and 78 are required for signal-induced phosphorylation and degradation of Cactus. I find that Slimb is the only F-box protein required for Toll-mediated Drosomycin induction. A Cactus kinase activity has been identified in a ∼250 kD protein complex. This Cactus kinase activity is infection inducible and is specific on the Cactus serine residues 74 and 78.; I find that DmIKK&egr; is not involved in the Toll-mediated embryogenesis or innate immune response in Drosophila. It functions in the biological processes different from its mammalian homologue. |
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