A family of protein kinases located upstream of the MAP kinases and responsible for their activation has been identified. The prototype member of this family, designated MAP kinase kinase, or MEK1, specifically phosphorylates the MAP kinase regulatory threonine and tyrosine residues present in the Thr-Glu-Tyr motif of ERK. A second MEK family member, MEK2, resembles MEK1 in its substrate specificity. MEK3 (or MKK3) functions to activate p38 MAP kinase, and MEK4 (also called SEK1 or MKK4) activates both p38 and JNK MAP kinases. MEK5 appears to specifically phosphorylate ERK5, whereas MEK6 phosphorylates p38 and p38b. MEK7 (or MKK7) phosphorylates and activates the JNK signal transduction pathway.
