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MAPK14 (p38 alpha) is a member of the stress-activated protein kinase class of MAPKs. The 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, which differ in their tissue expression and affinity for upstream activators and downstream effectors. When cells are exposed to tumor necrosis factor, interleukin-1, heat shock, or other activating stimuli, activation of MAPK kinase-3 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.
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