Fig. 1.

MAPK and JNK pathways regulate innate immunity and resistance to heavy metal toxicity. Depicted is the nematode C. elegans, highlighting the digestive tract of this worm. From left to right is the pharynx, intestine that spans almost the entire animal, and the posterior with the anus. (I) Once ingested, bacterium expressing a PFT interacts with the intestinal cells in an unknown manner, causing the up-regulation of the MAPK kinase kinase (MAPKKK) NSY-1, which activates the MAPK kinase SEK-1 to ultimately up-regulate the p38 MAPK PMK-1. Additionally, the PFT increases the activity of the JNK-related kinase KGB-1 by an unknown mechanism. The combined action of PMK-1 and KGB-1 results in the increased expression of ttm-1 and ttm-2, which function to increase resistance to PFT. (II) The ingestion of pathogenic bacterium, such as Pseudomonas aerugonisa, results in the interaction of bacterial products with the intestinal cells. This interaction, although unknown, results in the up-regulation of the MAPKKK pathway, although the impact of these events on the transcriptome is still not known. Unlike interaction with PFT (I), this interaction does not require the JNK kinase KGB-1. PMK-1 is negatively regulated by the VHP-1 dual specificity phosphatase (MKP7). (III) In response to heavy metal stress, the JNK-1 kinase KGB-1 becomes activated by MAPKKK pathway to regulate resistance to stress. This interaction does not require the p38 MAPK PMK-1, and again the influence on the transcriptome of activating this pathway is unknown. The activity of KGB-1 is negatively regulated by VHP-1.