High levels of Cr have been demonstrated to stimulate MAPKs while lower levels were more particular in triggering JNK in immortalized lung epithelial cells. Clonogenic death was mediated by neither sensitization to, nor inhibition of, Cr induced clonogenic lethality was observed after Erk inhibition by 100 uM PD98059 indicating a lack of Erk involvement in Cr. In addition, our present data show that both Erk silencing with siRNA and abrogation of Erk exercise by additional U0126 deubiquitinating enzyme inhibitor therapy in Erk silenced cells had no impact on Cr caused clonogenic lethality. Our present study may be the first record that activated Mek, in the absence of Erk action plays a part in the safety of normal human cells from genotoxin caused death. Indeed, we have shown that hyperphosphorylation of Mek after GW5074 treatment in addition to Mek1 over-expression substantially reduced Cr induced clonogenic lethality in HLFs. These observations suggest the presence of the book, Erk independent signaling pathway, possibly involving a kinase substrate downstream of Mek that is able to transduce its signal to modify cell growth/proliferation. As an alternative, Mek service alone may be sufficient to regulate cell growth upon genotoxin Endosymbiotic theory coverage. It is probable that Mek translocates to the nucleus and regulates cell growth or interacts with cytosolic effectors that control cell survival/growth in HLFs. Certainly, Mek translocation to the nucleus has been noted and its nuclear localization was offered by G2 M progression. A possible function of Mek translocation in enhanced clonogenic survival after genotoxin coverage happens to be under study within our laboratory. In sharp contrast, in the absence of genotoxin exposure, often exogenously expressed or chemically induced Mek activity had no influence on HLF clonogenic potential. In other words, while induced Mek activity all through Cr publicity ALK inhibitor was cytoprotective, it did not boost the basal amount of clonogenic potential when the cells weren’t challenged by Cr. This interesting phenomenon wasn’t discovered for Ras and c Raf activity. This original role of Mek activity during genotoxin stress might have resulted from the existence of a limit for activity or triggering phosphorylation level above which increased clonogenic emergency can be achieved in HLFs. In support of this theory, a quite recent study reported that an accurate threshold level of Myc is necessary for growth maintenance, whereupon there is a change in gene expression program from a state of expansion into a state of proliferative arrest and apoptosis. Again-this highlights the importance of level and duration of kinase activity in the Ras/MAPK axis throughout Cr insult and in the determination of cell fate. Duration of Mek and Akt activity as measured by the expression of these phosphorylated forms was administered after transfection with c/a Mek1 or c/an Akt1.