Two signal transducers that have been identified to be upstream of DON-induced MAPK activation are doublestranded RNA-(dsRNA) activated protein kinase (PKR) (Zhou et al., 2003b) and hematopoietic cell kinase (Hck) (Zhou et al., 2005b) . PKR is a widely distributed constitutively expressed serine/threonine protein kinase that can be activated by dsRNA, interferon, proinflammatory stimuli, cytokines, and oxidative stress (Garcia et al., 2006; Williams, 2001) . PKR also activates p53, p38, JNK, Nuclear Factor-kappaB, signal transducer and activator of transcription, and interferon regulatory factor-1 (Williams, 1999) . Hck, a member of Src kinase family, is expressed specifically in myelomonocytic cell lineages and transduces extracellular signals that regulate proliferation, differentiation, and migration (Ernst et al., 2002; Tsygankov, 2003) . Upon DON exposure, both PKR and Hck are activated prior to the MAPKs and their respective inhibitors suppress downstream MAPK activation (Zhou et al., 2005b) . Although crosstalk between PKR and Hck is not clearly understood, PKR appears to be required for Hck interaction with the ribosome in the human monocyte U937 cell line (Bae et al., 2010) .