| pubmed-article:19341436 | pubmed:abstractText | In the present study, we show that lethal toxin from Clostridium sordellii (TcsL-82) activates the three MAP kinase pathways, but that only a permeable and specific c-Jun-NH2-terminal kinase (JNK) inhibitor, JNK inhibitor II, prevents toxin-dependent actin depolymerization and cell rounding. We show that JNK activation is dependent on entry of the toxin N-terminal domain into the cytosol as bafilomycin A1, which prevents acidification of endocytic vesicle and subsequent cytosolic translocation of the toxin N-terminal domain, prevents JNK activation. Inhibition of JNK activity delays small GTPase glucosylation generated by N-terminal domain catalytic activity. Using a cell line mutant deficient in UDP-glucose, we observed that activation of JNK occurs even in the absence of small GTPase glucosylation and, thus, is independent of the toxin intrinsic catalytic activity. Facilitation of target glucosylation by JNK activation appeared to be restricted to TcsL-82 and was not a general feature of large clostridial toxins. Indeed, it was not observed with Toxin B from Clostridium difficile although this toxin also activates JNK. | lld:pubmed |
