Figure 1

Signaling pathways important for C. elegans intestinal defenses against bacterial proliferation. A. DAF-2 insulin/IGF-I like signaling pathway. Activation of the DAF-2 receptor results in the phosphorylation of the phosphatidyl inositol 3 kinase (AGE-1) which catalyses the conversion of phosphatidylinositol biphosphate (PiP₂) into phosphatidylinositol triphosphate (PiP₃). The kinases PDK-1 and AKT-1/AKT-2 are activated by PiP₃, which inhibits the transcription factor DAF-16. Relief of this inhibition leads to the expression of a set of stress response and antimicrobial genes. B. p38 MAPK pathway. PMK-1 is homologous to the mammalian p38 MAPK and acts downstream of NSY-1/MAKK kinase kinase and SEK-1/MAPK kinase. No interaction between TOL-1 and TIR-1 has been demonstrated. C. TGF-β pathway. The TGF-β homologue DBL-1 binds to the heterodimeric receptor SMA-6/DAF-4 and signals through the Smad proteins SMA-2, SMA-3 and SMA-4, which activate the transcription of genes involved in regulation of body size and innate immunity. The expression of lysozyme gene lys-1 is under the control of the p38 MAPK pathway and the DBL-1/TGF-β pathway. D. Mitochondrial enzymes. CLK-1 is an enzyme required for the biosynthesis of ubiquinoe CoQ9, an acceptor of electrons from both complexes I and II in C. elegans cells. Decreased complex I-dependent respiration of clk-1 mutants leads to decreased ROS production with lengthening lifespan and slowing development. TRX-1 is a mitochondrial oxidoreductase with important roles in lifespan regulation and oxidative stress response.