Lange-Carter C A, Pleiman C M, Gardner A M, Blumer K J, Johnson G L
Division of Basic Sciences, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Science. 1993 Apr 16;260(5106):315-9. doi: 10.1126/science.8385802.
Mitogen-activated protein kinases (MAPKs) are rapidly phosphorylated and activated in response to various extracellular stimuli in many different cell types. Such regulation of MAPK results from sequential activation of a series of protein kinases. The kinases that phosphorylate MAPKs, the MAP kinase kinases (MEKs) are also activated by phosphorylation. MEKs are related in sequence to the yeast protein kinases Byr1 (from Schizosaccharomyces pombe) and Ste7 (from Saccharomyces cerevisiae), which function in the pheromone-induced signaling pathway that results in mating. Byr1 and Ste7 are in turn regulated by the protein kinases Byr2 and Ste11. The amino acid sequence of the mouse homolog of Byr2 and Ste11, denoted MEKK (MEK kinase), was elucidated from a complementary DNA sequence encoding a protein of 672 amino acid residues (73 kilodaltons). MEKK was expressed in all mouse tissues tested, and it phosphorylated and activated MEK. Phosphorylation and activation of MEK by MEKK was independent of Raf, a growth factor-regulated protein kinase that also phosphorylates MEK. Thus, MEKK and Raf converge at MEK in the protein kinase network mediating the activation of MAPKs by hormones, growth factors, and neurotransmitters.
丝裂原活化蛋白激酶（MAPKs）在许多不同细胞类型中，会因各种细胞外刺激而迅速发生磷酸化并被激活。MAPK的这种调节是由一系列蛋白激酶的顺序激活所导致的。使MAPKs磷酸化的激酶，即丝裂原活化蛋白激酶激酶（MEKs），也通过磷酸化被激活。MEKs在序列上与酵母蛋白激酶Byr1（来自粟酒裂殖酵母）和Ste7（来自酿酒酵母）相关，它们在导致交配的信息素诱导信号通路中发挥作用。Byr1和Ste7又受蛋白激酶Byr2和Ste11的调节。从小鼠中与Byr2和Ste11同源的蛋白（称为MEKK，即MEK激酶）的氨基酸序列，是从一个编码672个氨基酸残基（73千道尔顿）的互补DNA序列中推导出来的。MEKK在所有测试的小鼠组织中均有表达，并且它能使MEK磷酸化并激活MEK。MEKK对MEK的磷酸化和激活不依赖于Raf，Raf是一种受生长因子调节的蛋白激酶，它也能使MEK磷酸化。因此，在由激素、生长因子和神经递质介导的MAPKs激活的蛋白激酶网络中，MEKK和Raf在MEK处汇聚。
