Aouadi M, Binetruy B, Caron L, Le Marchand-Brustel Y, Bost F
Inserm U568, faculté de médecine, Université de Nice Sophia-Antipolis, avenue de Valombrose, 06107 Nice cedex, France.
Biochimie. 2006 Sep;88(9):1091-8. doi: 10.1016/j.biochi.2006.06.003. Epub 2006 Jun 27.
The ERK, p38MAPK, JNK mitogen-activated protein kinases (MAPKs) are intracellular signaling pathways that play a pivotal role in many essential cellular processes such as proliferation and differentiation. These cascades are activated by a large variety of stimuli and display a high degree of homology. So far, seven MAPK isoforms have been invalidated in mice leading to the discovery of their important functions in development and differentiation. As we could expect because of their multiple and specific properties in vitro, knockout (KO) of MAPK pathways leads to distinct phenotypes in mice. Surprisingly, into a given cascade, KOs of the various isoforms assign specific non-redundant biological functions to each isoform, without compensation by the others. These results emphasize the notion that, although initiated by the same external stimuli, these intracellular cascades activate kinase isoforms each with its own specific role.
细胞外信号调节激酶（ERK）、p38丝裂原活化蛋白激酶（p38MAPK）和c-Jun氨基末端激酶（JNK）丝裂原活化蛋白激酶（MAPK）是细胞内信号传导途径，在许多重要的细胞过程如增殖和分化中起关键作用。这些级联反应由多种刺激激活，并显示出高度的同源性。到目前为止，七种MAPK亚型在小鼠中已被敲除，从而发现了它们在发育和分化中的重要功能。由于它们在体外具有多种特定特性，正如我们所预期的那样，MAPK途径的基因敲除（KO）在小鼠中导致了不同的表型。令人惊讶的是，在给定的级联反应中，各种亚型的基因敲除赋予每个亚型特定的非冗余生物学功能，而不会被其他亚型代偿。这些结果强调了这样一个概念，即尽管这些细胞内级联反应由相同的外部刺激启动，但它们激活的激酶亚型各自具有特定的作用。
