Balance between MKK6 and MKK3 Mediates p38 MAPK Associated Resistance to Cisplatin in NSCLC
Figure 5
Balance between MKK6 and MKK3 mediates p38 MAPK associated resistance to cisplatin.
Upper panel: In the absence of stimuli (left), sensitive cells display high basal levels of MKK6 and low basal levels of MKK3 which maintain a normal basal activity of p38 MAPK. When cells are exposed to cDDP (right), the existing molecules of MKK3 are phosphorylated and then they are able to activate p38 MAPK, provoking the death of the cells. Lower panel: In basal conditions (left), resistant cells express elevated levels of MKK3 which is indeed intrinsically phosphorylated. As a consequence, resistant cells show an aberrant basal activity of p38 MAPK which is controlling MKK6 by decreasing its RNA levels. As consequence of the constitutive activation of MKK3, cells are unable to respond to cDDP treatment (right), surviving after exposure to the drug.