Mitogen-activated protein kinases (MAPK), including ERK1/2, p38, and JNK1/2, are important regulators of cell function. The ERK MAPKs are most frequently activated by mitogenes, whereas the JNK and p38 MAPKs are strongly responsive to stress and inflammatory signals. The MAPKs are activated through multiple intracellular phosphorylation cascade events. The core unit includes MAPKKKs and MAPKKs. MEK1 and MEK2 are dual-specificity proteins kinases. MEKs activates ERK1 and ERK2 by phosphorylating both threonine and tyrosine residues at sites located within the activation loop of kinase subdomain VIII.