However, torilin did not affect MyD88, IRAK1, and TRAF6 downstream of TLR4 but suppressed the signaling effects thereafter at the level of MAP3K complexes.
Caption: FIGURE 6: Torilin suppresses LPS-induced IKK and MAP3K complex activation and inhibits the TAK1 interaction with the components of MAPK and NF-[kappa]B signaling pathways.
(21,22) MAPKs are phosphorylated and activated by MAPK-kinases (MAPKKs or MAP2Ks), which in turn are phosphorylated and activated by MAPKK-kinases (MAPKKK or MAP3Ks
ASK1 was identified as a MAP3K that activates the MAP kinase kinase 4 (MKK4)/MKK7-JNK and MKK3/MKK6-p38 pathways.
(26,27) Mammals also express ASK2, which is another MAP3K highly homologous to ASK1.
(21) Thus far, MAP3K kinases (MAP4Ks) that directly activate ASK1 by phosphorylating Thr838 of ASK1 have not been identified.
Johnson, "Integrated activation of MAP3Ks
balances cell fate in response to stress," Journal of Cellular Biochemistry, vol.
As a serine/threonine kinase belonging to the mitogen activated protein kinase kinase kinase (MAP3K) family, ASK1 has been reported to play a critical role in reactive oxygen species (ROS)-induced apoptosis in various cell types and oxidative stress-related diseases such as D-galactosamine/lipopolysaccharide induced hepatotoxicity and cardiovascular disease [21-24].
Since MAPKs could be regulated upstream by the MAPK kinase kinase kinase (MAP3K) and p38 MAPK could act as the target of ASK1, we investigated the effect of contrast media on activation of ASK1, a member of MAP3K family [20, 41].