p38 MAPK cascade regulates a variety of cellular responses to stress, inflammation and other signals. p38 MAPK is relatively inactive in the nonphosphorylated form and becomes rapidly activated by dual phosphorylation of a Thr-Gly-Tyr motifs. There are four isoforms of p38 MAPK, α, β, γ and δ, which differ in their tissue expression and affinity for upstream activators and downstream effectors. When cells are exposed to tumor necrosis factor-α, interleukin-1, heat shock, or other activating stimuli, activation of MAPK kinase-3 and –6 occurs by phosphorylation. Activated MAPK kinase-3/6 phosphorylate each residue of Thr180 and Tyr182 in p38 MAPK. Phospho-p38 MAPK activates ATF- 2, CHOP-1, MEF-2 and other transcription factors through phosphorylation.