A DIVERGENCE IN THE MAP KINASE REGULATORY NETWORK DEFINED BY MEK KINASE AND RAF
A DIVERGENCE IN THE MAP KINASE REGULATORY NETWORK DEFINED BY MEK KINASE AND RAF
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DOI：
10.1126/science.8385802
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发表时间：
1993-04-16
期刊：
影响因子：
56.9
通讯作者：
JOHNSON, GL
中科院分区：
文献类型：
--
作者：
LANGECARTER, CA;PLEIMAN, CM;JOHNSON, GL
丝裂原活化蛋白激酶（MAPK）在许多不同细胞类型中响应于各种细胞外刺激而迅速磷酸化和活化。MAPK的这种调节是由一系列蛋白激酶的顺序激活引起的。磷酸化MAPK的激酶，MAP激酶激酶（MEK）也被磷酸化激活。MEK在序列上与酵母蛋白激酶Byr 1（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的信号传导途径中起作用。Byr 1和Ste7依次由蛋白激酶Byr 2和Ste11调节。从编码672个氨基酸残基（73千道尔顿）的蛋白质的互补DNA序列中阐明了Byr 2和Ste11的小鼠同源物（表示为MEKK（MEK激酶））的氨基酸序列。MEKK在所有测试的小鼠组织中表达，并且其磷酸化和活化MEK。磷酸化和活化的MEK的MEKK是独立的Raf，生长因子调节的蛋白激酶，也磷酸化MEK。因此，MEKK和Raf在介导由激素、生长因子和神经递质激活MAPK的蛋白激酶网络中会聚于MEK。
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.