Mitogen-activated protein kinase (MAPK)
Mitogen-activated protein kinase (MAPK)
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DOI：
10.1097/01.ccm.0000191714.39495.a6
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发表时间：
2005-12-01
影响因子：
8.8
通讯作者：
Maier, RV
中科院分区：
文献类型：
--
作者：
Cuschieri, J;Maier, RV
在分子水平上，免疫状态通过一系列相互关联和严格控制的细胞内信号通路(1，2)来控制。这在一定程度上是通过蛋白质磷酸化激活或去激活调节蛋白来实现的。高度保守的丝裂原活化蛋白激酶(MAPK)家族是通过将细胞外信号转化为细胞反应来调节细胞的主要激酶家族之一(3)。该家族的三个重要成员是细胞外信号调节激酶(ERK)、p38和c-jun氨基末端激酶(JNK)。经典的MAPK级联由三个顺序的细胞内蛋白激酶激活步骤组成，当第一个成员MAPK激酶(MAPKKK)被激活时启动(图1)。MAPKKK是一种蛋白激酶，可磷酸化并激活MAPK(MAPKK)，这种激活之后是特定的MAPK的激活。MAPK是一种脯氨酸导向的蛋白激酶，这意味着它们可以磷酸化与Pro相邻的丝氨酸或苏氨酸残基。通过这种方式，MAPK激活了许多蛋白激酶、核蛋白和转录因子，导致了下游的信号转导。MAPK级联的激活很快，使细胞能够以调节的方式对环境变化做出反应。
At a molecular level, the immune state is controlled through an exhaustive array of interconnected and tightly controlled series of intracellular signaling pathways (1, 2). This is achieved, in part, by activating or deactivating regulatory proteins through protein phosphorylation. The highly conserved mitogen-activated protein kinase (MAPK) family is one of the major kinase families that regulate cells by transducing extracellular signals into cellular responses (3). Three important members of this family are the extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). Each is similarly activated by dual phosphorylation on adjacent threonine and tyrosine residues.The classic MAPK cascade consists of three sequential intracellular protein kinase activation steps and is initiated when the first member, MAPK kinase kinase (MAPKKK), is activated (Fig. 1). MAPKKK is a protein kinase that phosphorylates and activates MAPK kinase (MAPKK), and this activation is followed by activation of the specific MAPK. MAPKs are proline-directed protein kinases, meaning that they phosphorylate serine or threonine residues that are neighbors to proline. In this manner, MAPKs activate numerous protein kinases, nuclear proteins, and transcription factors, leading to downstream signal transduction. Activation of the MAPK cascade is rapid and enables cells to respond to environmental changes in a regulated fashion.