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 MEK-1, specifically phosphorylates
the MAP kinase regulatory threonine and tyrosine residues present in the
Thr-Glu-Tyr motif of ERK. A second MEK family member, MEK-2, resembles
MEK-1 in its substrate specificity. MEK-3 (or MKK3) functions to activate
p38 MAP kinase, and MEK-4 (also called SEK1 or MKK4) activates both p38
and JNK MAP kinases. MEK-5 appears to specifically phosphorylate ERK 5,
whereas MEK-6 phosphorylates p38 and p38β. MEK-7 (or MKK7) phosphorylates
and activates the JNK signal transduction pathway. Phosphorylation on
Ser/Thr by MAP kinase kinase kinases (RAF or MEKK1) positively regulates
the kinase activity.