MAPK3 and skin cancer: As an example, in macrophages isolated from whole-body Tpl2-deficient mice, JNK and p38 activation in response to LPS was sustained to compensate for the decrease of ERK1/2.35 Similarly, in a chemically induced mouse skin cancer, oncogenic effects of Tpl2 ablation were mediated by increased NF-κB activity.36 Hence, inhibiting Tpl2 kinase activity, rather than inactivating its expression, may be a more efficient strategy to protect β-cells from proinflammatory cytokines.