“…Once in the cytoplasm, the A 1 -fragment escapes routing to the proteasome and inhibits protein synthesis by the catalytic removal of a single adenine residue from the 28S rRNA (reviewed in Johannes and Römer, 2010; Sandvig et al ., 2010). In addition to mediating protein synthesis inhibition, Stxs activate multiple signaling pathways including: i) signaling through src kinases, PI3K, Akt and mTOR (Katagiri et al , 1999, Zanchi et al , 2008, Cherla et al , 2009); ii) activation of MAPKs (Foster et al , 2002, Smith et al , 2003) and their upstream kinases PKR, MK-2 and ZAK (Gray et al , 2008, Jandhyala et al , 2008, Saenz et al , 2009); iii) activation of NF-κB and AP-1 transcription factors (Sakiri et al , 1998, Zoja et al, 2002); and iv) prolonged activation of the ER stress response (Lee et al , 2009, Lee et al , 2010). Signaling through these pathways has been shown to be important in toxin internalization and routing, induction of cytokine/chemokine expression, and the induction of apoptosis.…”