Raman M, Chen W, Cobb M H
Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Oncogene. 2007 May 14;26(22):3100-12. doi: 10.1038/sj.onc.1210392.
Mitogen-activated protein kinases (MAPKs) regulate diverse cellular programs including embryogenesis, proliferation, differentiation and apoptosis based on cues derived from the cell surface and the metabolic state and environment of the cell. In mammals, there are more than a dozen MAPK genes. The best known are the extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK(1-3)) and p38(alpha, beta, gamma and delta) families. ERK3, ERK5 and ERK7 are other MAPKs that have distinct regulation and functions. MAPK cascades consist of a core of three protein kinases. Despite the apparently simple architecture of this pathway, these enzymes are capable of responding to a bewildering number of stimuli to produce exquisitely specific cellular outcomes. These responses depend on the kinetics of their activation and inactivation, the subcellular localization of the kinases, the complexes in which they act, and the availability of substrates. Fine-tuning of cascade activity can occur through modulatory inputs to cascade component from the primary kinases to the scaffolding accessory proteins. Here, we describe some of the properties of the three major MAPK pathways and discuss how these properties govern pathway regulation and activity.
丝裂原活化蛋白激酶（MAPK）根据源自细胞表面以及细胞代谢状态和环境的信号，调节包括胚胎发生、增殖、分化和凋亡在内的多种细胞程序。在哺乳动物中，有十几种MAPK基因。最知名的是细胞外信号调节激酶1和2（ERK1/2）、c-Jun氨基末端激酶（JNK(1-3)）和p38（α、β、γ和δ）家族。ERK3、ERK5和ERK7是其他具有不同调节和功能的MAPK。MAPK级联由三种蛋白激酶组成核心。尽管该途径的结构看似简单，但这些酶能够对大量令人眼花缭乱的刺激做出反应，从而产生极其特异的细胞结果。这些反应取决于它们激活和失活的动力学、激酶的亚细胞定位、它们发挥作用的复合物以及底物的可用性。级联活性的微调可以通过从初级激酶到支架辅助蛋白对级联组件的调节输入来实现。在这里，我们描述了三种主要MAPK途径的一些特性，并讨论了这些特性如何控制途径的调节和活性。
