Zheng C F, Guan K L
Department of Biological Chemistry, University of Michigan, Ann Arbor 48109.
J Biol Chem. 1993 May 25;268(15):11435-9.
Mitogen-induced signal transduction is mediated by a cascade of protein phosphorylation and dephosphorylation. One of the immediate responses of mitogen stimulation is the activation of a family of protein kinases known as mitogen-activated protein kinase or extracellular signal-regulated kinase (ERK). MEK (MAP kinase or ERK kinase) is the immediate upstream activator kinase of ERK. Two cDNAs, MEK1 and MEK2, were cloned and sequenced. MEK1 and MEK2 encode 393 and 400 amino acid residues, respectively. The human MEK1 shares 99% amino acid sequence identity with the murine MEK1 and 80% with human MEK2. Both MEK1 and MEK2 were expressed in Escherichia coli and shown to be able to activate recombinant human ERK1 in vitro. The purified MEK2 protein stimulated threonine and tyrosine phosphorylation on ERK1 and concomitantly activated ERK1 kinase activity more than 100-fold. The recombinant MEK2 showed lower activity as an ERK activator as compared with MEK purified from tissue. However, the recombinant MEK2 can be activated by serum-stimulated cell extract in vitro. MEKs, in a manner similar to ERKs, are likely to consist of a family of related proteins playing critical roles in signal transduction.
有丝分裂原诱导的信号转导由一系列蛋白质磷酸化和去磷酸化介导。有丝分裂原刺激的即时反应之一是激活一类称为丝裂原活化蛋白激酶或细胞外信号调节激酶（ERK）的蛋白激酶。MEK（MAP激酶或ERK激酶）是ERK的直接上游激活激酶。克隆并测序了两个cDNA，即MEK1和MEK2。MEK1和MEK2分别编码393和400个氨基酸残基。人MEK1与鼠MEK1的氨基酸序列同一性为99%，与人MEK2的同一性为80%。MEK1和MEK2均在大肠杆菌中表达，并显示在体外能够激活重组人ERK1。纯化的MEK2蛋白刺激ERK1上的苏氨酸和酪氨酸磷酸化，并同时激活ERK1激酶活性超过100倍。与从组织中纯化的MEK相比，重组MEK2作为ERK激活剂的活性较低。然而，重组MEK2可在体外被血清刺激的细胞提取物激活。MEK与ERK类似，可能由在信号转导中起关键作用的相关蛋白家族组成。
