Brott B K, Alessandrini A, Largaespada D A, Copeland N G, Jenkins N A, Crews C M, Erikson R L
Department of Cellular and Developmental Biology, Harvard University, Cambridge, Massachusetts 02138.
Cell Growth Differ. 1993 Nov;4(11):921-9.
MEK1 is a dual specificity kinase that phosphorylates and activates the Erk/MAP kinases Erk-1 and Erk-2 by phosphorylating them on threonine and tyrosine. We report the cloning of a second MEK-like complementary DNA, Mek2, which predicts a protein of a molecular weight of 44,500. The MEK2 protein bears substantial sequence homology to MEK1, except at its amino terminus, and at a proline-rich region insert between the conserved kinase subdomains 9 and 10. MEK1 and MEK2 are shown to be encoded by different genes and are located on murine chromosomes 9 and 10, respectively. Northern analysis indicates that Mek2 is expressed at low levels in adult mouse brain and heart tissue, and at higher levels in other tissues examined. Low expression levels of Mek2 in brain tissue are in contrast to the high levels of Mek1 expressed in brain. Mek2 is expressed at high levels in neonatal brain, however. Recombinant MEK2 produced in bacteria phosphorylates a kinase-inactive Erk-1 on tyrosine and threonine, whereas a kinase-inactive mutant MEK2 does not. These findings suggest that MEK2 is a member of a multigene family.
MEK1是一种双特异性激酶，它通过在苏氨酸和酪氨酸上磷酸化来激活Erk/MAP激酶Erk-1和Erk-2。我们报道了第二个MEK样互补DNA（Mek2）的克隆，它预测的蛋白质分子量为44,500。MEK2蛋白与MEK1具有大量的序列同源性，除了其氨基末端以及保守激酶亚结构域9和10之间富含脯氨酸的区域插入处。MEK1和MEK2显示由不同基因编码，分别位于小鼠的9号和10号染色体上。Northern分析表明，Mek2在成年小鼠脑和心脏组织中低水平表达，而在其他检测组织中高水平表达。Mek2在脑组织中的低表达水平与脑中MEK1的高表达水平形成对比。然而，Mek2在新生脑中高水平表达。在细菌中产生的重组MEK2在酪氨酸和苏氨酸上磷酸化无激酶活性的Erk-1，而无激酶活性的突变体MEK2则不能。这些发现表明MEK2是一个多基因家族的成员。
