| A family of protein kinases 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 amino acid motif just upstream of a conserved APE amino acid sequence. A second MEK family member, MEK-2, resembles MEK-1 in its substrate specificity. Additional MEK proteins include MEK-3 (alternatively designated MKK-3), which functions to activate the MAP kinase related protein p38 MAP kinase, and MEK-4 (alternatively designated SEK1 or MKK-4), which activates both p38 MAP kinase and JNK. A fifth member of this family, MEK-5, appears to specifically phosphorylate ERK 5, whereas MEK-6 phosphorylates p38 and p38(beta). MEK-7 (or MKK-7) phosphorylates and activates the JNK signal transduction pathway. |
