Increased kinase suppressor of RAS activity in inflamed intestinal mucosa

H-Ras-specific activation of NF-κB protects NIH 3T3 cells against stimulus-dependent apoptosis

“…Inhibition of MEK1 or PI3-kinase failed to induce a significant apoptosis in response to TNFa or to cooperate with SN50-or staurosporine-induced apoptosis. This was not the case of epithelial cells where a cooperative response was observed between the NF-kB and MEK1 pathways (Yan et al, 2001). In addition to these pathways, it has been described that early activation of caspases can cleave targets that act in turn as antiapoptotic molecules.…”

“…Similar results were obtained when cells were treated with MG132, an inhibitor of the proteasome activity (not shown; see Figure 4), and therefore of NF-kB activation. Previous work showed that in intestinal epithelial cells inhibitors of both MEK1/ERK and NF-kB activation cooperate to induce apoptosis in response to TNFa through a mechanism dependent on kinase suppressor of Ras (KSR) (Yan et al, 2001). At the same time, the contribution of the PI3-kinase/PKB to inhibit apoptosis has been well documented (Grana et al, 2002).…”