We first investigated whether the ire-1-xbp-1 pathway plays a role in the PFT-induced activation of p38 by comparing the activation of the p38 MAPK in wild-type and xbp1(zc12) animals. We find that addition of Cry5B to wild-type C. elegans results in an increase in phosphorylated p38, indicating the p38 pathway is activated by a PFT in C. elegans just as it is in mammalian cells [20] ( Figure 5A ). We find that p38 activation occurs normally in xbp-1(zc12) mutant animals ( Figure 5A ), indicating that the UPR is not required for activation of p38 MAPK pathway in response to PFT. We extended this result using ttm-2, a downstream transcriptional target of the p38 MAPK pathway in response to Cry5B and a gene required for normal defense against Cry5B PFT [6] . Upregulation of ttm-2 mRNA was dependent on the p38 MAPK pathway but not dependent on xbp-1 ( Figure 5F ).