The MAP Kinase Signaling Cascades: A System of Hundreds of Components Regulates a Diverse Array of Physiological Functions
The MAP Kinase Signaling Cascades: A System of Hundreds of Components Regulates a Diverse Array of Physiological Functions
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DOI：
10.1007/978-1-60761-795-2_1
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发表时间：
2010-01-01
期刊：
影响因子：
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通讯作者：
Seger, Rony
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文献类型：
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作者：
Keshet, Yonat;Seger, Rony
丝裂原活化蛋白激酶（MAPK）级联中激酶的顺序激活是一种常见的、进化保守的信号转导机制。在过去的20年中，已经确定了四个MAPK级联，这些级联通常根据作为每个级联的中心构件的MA P K组件来命名。这些是细胞外信号调节激酶1/2（ERK 1/2）、c-Jun N-末端激酶（JNK）、p38和ERKS级联。这些级联中的每一个都由称为MAPK、MAPKK和MAP 3 K的三层蛋白激酶的核心模块组成，并且通常还包括两个额外的层，上游MAP 4K和下游MAPKAPK，其可以在某些细胞系或刺激中完成每个级联的五层。通过每个级联的信号传输是由顺序磷酸化和顺序层中组分的激活介导的。这些级联在传递各种细胞外信号中合作，从而控制大量不同的甚至相反的细胞过程，例如增殖、分化、存活、发育、应激反应和凋亡。调节每个级联的特异性的一种方式是通过在不同级联的每一层中存在几个不同的组分。大约70个基因，每个基因翻译成几种选择性剪接的同种型，编码整个MAPK系统，并允许广泛的级联功能。这些组件，他们的监管，以及他们的参与与其他机制一起在确定信号特异性的MAPK级联反应中进行了描述。MAPKs信号的错误调节通常会导致癌症和糖尿病等疾病;因此，研究特异性决定机制可能会更好地理解这些信号相关疾病。
Sequential activation of kinases within the mitogen-activated protein (MAP) kinase (MAPK) cascades is a common, and evolutionary-conserved mechanism of signal transduction. Four MAPK cascades have been identified in the last 20 years and those are usually named according to the MA P K components that are the central building blocks of each of the cascades. These arc the extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-Terminal kinase (JNK), p38, and ERKS cascades. Each of these cascades consists of a core module of three tiers of protein kinases termed MAPK, MAPKK, and MAP3K, and often two additional tiers, the upstream MAP4K and the downstream MAPKAPK, which can complete five tiers of each cascade in certain cell lines or stimulations. The transmission of the signal via each cascade is mediated by sequential phosphorylation and activation of the components in the sequential tiers. These cascades cooperate in transmitting various extracellular signals and thus control a large number of distinct and even opposing cellular processes such as proliferation, differentiation, survival, development, stress response, and apoptosis. One way by which the specificity of each cascade is regulated is through the existence of several distinct components in each tier of the different cascades. About 70 genes, which are each translated to several alternatively spliced isoforms, encode the entire MAPK system, and allow the wide array of cascade's functions. These components, their regulation, as well as their involvement together with other mechanisms in the determination of signaling specificity by the MAPK cascade is described in this review. Mis-regulation of the MAPKs signals usually leads to diseases such as cancer and diabetes; therefore, studying the mechanisms of specificity-determination may lead to better understanding of these signaling-related diseases.