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Activation of JNK by MLK3/MLKs. MLK3 is activated by its agonist TNFα and ceramide. The activation of MLK3 phosphorylates MEK members MKK4 and MKK7. The activated MKK4 and MKK7 phosphorylate and activate JNK that ultimately regulates AP-1–mediated gene expression. The pan-MLK inhibitors CEP-1347 and CEP-11004 are reported to block MLK-mediated downstream signaling.
