Robbins D J, Zhen E, Cheng M, Xu S, Vanderbilt C A, Ebert D, Garcia C, Dang A, Cobb M H
J Am Soc Nephrol. 1993 Nov;4(5):1104-10. doi: 10.1681/ASN.V451104.
The extracellular signal-regulated kinases ERK1 and ERK2 are 43- and 41-kd enzymes activated by many extracellular cues. They lie within a protein kinase cascade that is used to achieve many cellular responses. In addition to the wide variety of regulatory contexts in which they are activated, they phosphorylate important regulatory proteins, including receptors, transcription factors, cytoskeletal proteins, and other protein kinases. Thus, the stimulation of this kinase cascade is thought to have a pleiotropic action. ERK1 and ERK2 are controlled by phosphorylation on threonine and tyrosine. To understand the regulatory mechanisms, wild-type and mutant ERKs were expressed in bacteria and phosphorylated with MEK, the enzyme that is upstream of ERKs. Wild-type proteins could be activated 500- to 1,000-fold in vitro by MEK. ERK3, an enzyme of 62 kd and only 50% identical to ERK1 and ERK2 in the catalytic core, was also phosphorylated by MEK in vitro. This suggests that all three of these enzymes are targets of common signaling pathways.
细胞外信号调节激酶ERK1和ERK2是43千道尔顿和41千道尔顿的酶，可被多种细胞外信号激活。它们处于一个用于实现多种细胞反应的蛋白激酶级联反应之中。除了在多种被激活的调控环境中发挥作用外，它们还能使重要的调控蛋白磷酸化，这些蛋白包括受体、转录因子、细胞骨架蛋白以及其他蛋白激酶。因此，这种激酶级联反应的激活被认为具有多效性作用。ERK1和ERK2受苏氨酸和酪氨酸磷酸化的调控。为了解其调控机制，野生型和突变型ERK在细菌中表达，并由ERK上游的酶MEK进行磷酸化。野生型蛋白在体外可被MEK激活500至1000倍。ERK3是一种62千道尔顿的酶，其催化核心与ERK1和ERK2仅有50%的同源性，在体外也能被MEK磷酸化。这表明这三种酶都是共同信号通路的靶点。
