We next analyzed the reverse relationship between the ire-1-xbp-1 and the p38 MAPK pathways, namely whether the p38 MAPK pathway is required for PFT-induced activation of the ire-1-xbp-1 pathway. We find that activation of the ire-1-xbp-1 pathway in response to PFT is dependent on the p38 MAPK pathway, namely on sek-1, the MAPK kinase (MAPKK) gene upstream of p38, and on pmk-1, the p38 MAPK downstream of sek-1 ( Figure 5 ). We find that increased splicing (activation) of xbp-1 in response to Cry5B does not occur in sek-1(km4) MAPKK mutant animals ( Figure 5B) . Quantitatively, at the 3 h time point the spliced form of xbp-1 is induced 1.9 fold in animals with an intact p38 MAPK pathway and depressed 1.8 fold in sek-1(km4) MAPKK mutant animals relative to untreated controls. However, sek-1 is not absolutely required for splicing of xbp-1 since, in response to tunicamycin, splicing of xbp-1 is normal in sek-1(km4) mutant animals ( Figure 5C ). In agreement with these results, we find that in vivo activation of the downstream target of the ire-1-xbp-1 pathway, hsp-4::GFP, by Cry5B within intestinal cells does not occur in pmk-1(km25) p38 MAPK mutant animals ( Figure 5D ), whereas activation of hsp-4::GFP by tunicamycin does occur normally in pmk-1(km25) mutant animals ( Figure 5E ).