The PAKs come of age: Celebrating 18 years of discovery.
The PAKs come of age: Celebrating 18 years of discovery.
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DOI：
10.4161/cl.22084
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发表时间：
2012-04-01
期刊：
影响因子：
--
通讯作者：
Manser E
中科院分区：
文献类型：
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作者：
Field J;Manser E
蛋白激酶是参与调节大多数生理反应的多功能信号分子。p21激活的激酶（PAK）可以被小GTP酶Rac和Cdc42直接激活，并且是这些Rho蛋白的最佳表征的下游效应物之一。从原生动物到哺乳动物，PAKS的结构、底物特异性和功能作用在进化上是保守的。脊椎动物PAK对细胞骨架重塑和粘着斑组装特别重要，从而有助于动态过程，如细胞迁移和突触可塑性。本期《细胞物流》重点介绍了PAK激酶家族，其中有十篇由目前在该领域工作的研究人员撰写的评论。在这篇介绍性的概述中，我们重点介绍了一些关于PAK生物化学和生物学的最有趣的最新发现。本期的综述涵盖了一系列主题，包括PAK 1和PAK 4的原子结构，通过敲除研究评估的它们在动物中的作用，以及PAK如何可能导致癌症和神经退行性疾病。PAK抑制剂的出现将验证目前的临床前研究，表明阻断PAK活性将对人类健康做出积极贡献。
Protein kinases are versatile signaling molecules that are involved in the regulation most physiological responses. The p21-activated kinases (PAKs) can be activated directly by the small GTPases Rac and Cdc42 and are among the best characterized downstream effectors of these Rho proteins. The structure, substrate specificity and functional role of PAKS are evolutionarily conserved from protozoa to mammals. Vertebrate PAKs are particularly important for cytoskeletal remodeling and focal adhesion assembly, thereby contributing to dynamic processes such as cell migration and synaptic plasticity. This issue of Cellular Logistics focuses on the PAK family of kinases, with ten reviews written by researchers currently working in the field. Here in this introductory overview we highlight some of the most interesting recent discoveries regarding PAK biochemistry and biology. The reviews in this issue cover a range of topics including the atomic structures of PAK1 and PAK4, their role in animals as assessed by knockout studies, and how PAKs are likely to contribute to cancer and neurodegenerative diseases. The promise remains that PAK inhibitors will emerge that validate current pre-clinical studies suggesting that blocking PAK activity will positively contribute to human health.