Glycogen synthase kinase-3 (GSK3): regulation, actions, and diseases.
Glycogen synthase kinase-3 (GSK3): regulation, actions, and diseases.
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DOI：
10.1016/j.pharmthera.2014.11.016
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发表时间：
2015-04
影响因子：
13.5
通讯作者：
Jope, Richard S.
中科院分区：
文献类型：
--
作者：
Beurel, Eleonore;Grieco, Steven F.;Jope, Richard S.
关键词：
糖原合成酶激酶-3（GSK 3）可能是大多数细胞中最繁忙的激酶，有超过100种已知底物需要处理。GSK 3如何保持控制以选择性磷酸化每种底物，以及为什么GSK 3承担如此大的责任在进化上是有利的？GSK 3必须特别适应于将新的底物纳入其库，我们讨论了GSK 3的独特性质，这可能有助于其在多个信号通路中发挥作用的能力。调节GSK 3的机制（主要是翻译后修饰，底物引发，细胞运输，蛋白质复合物）已被审查之前，所以在这里，我们专注于新发现的复杂性，在这些机制，这些调节机制如何有助于GSK 3的能力，选择哪些底物磷酸化，以及如何这些机制可能有助于其适应性作为新的底物进化。本文综述了目前对GSK 3调节机制的认识，以及GSK 3作用的新课题，特别是其与受体的相互作用和受体偶联信号转导事件，以及GSK 3 α和GSK 3 β两种亚型的差异作用和调节。GSK 3的另一个显著特征是其参与许多流行疾病，包括精神和神经疾病、炎性疾病、癌症等。我们解决的可行性，靶向GSK 3治疗，并提供其参与的病因和治疗的几种疾病的更新。
Glycogen synthase kinase-3 (GSK3) may be the busiest kinase in most cells, with over 100 known substrates to deal with. How does GSK3 maintain control to selectively phosphorylate each substrate, and why was it evolutionarily favorable for GSK3 to assume such a large responsibility? GSK3 must be particularly adaptable for incorporating new substrates into its repertoire, and we discuss the distinct properties of GSK3 that may contribute to its capacity to fulfill its roles in multiple signaling pathways. The mechanisms regulating GSK3 (predominantly post-translational modifications, substrate priming, cellular trafficking, protein complexes) have been reviewed previously, so here we focus on newly identified complexities in these mechanisms, how each of these regulatory mechanism contributes to the ability of GSK3 to select which substrates to phosphorylate, and how these mechanisms may have contributed to its adaptability as new substrates evolved. The current understanding of the mechanisms regulating GSK3 is reviewed, as are emerging topics in the actions of GSK3, particularly its interactions with receptors and receptor-coupled signal transduction events, and differential actions and regulation of the two GSK3 isoforms, GSK3α and GSK3β. Another remarkable characteristic of GSK3 is its involvement in many prevalent disorders, including psychiatric and neurological diseases, inflammatory diseases, cancer, and others. We address the feasibility of targeting GSK3 therapeutically, and provide an update of its involvement in the etiology and treatment of several disorders.
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影响因子：
4.8
作者：
Beurel E
通讯作者：
Beurel E
影响因子：
4.8
作者：
Beurel, Eleonore;Jope, Richard S.
通讯作者：
Jope, Richard S.
DOI：
10.4049/jimmunol.1003511
发表时间：
2011-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Beurel E;Yeh WI;Michalek SM;Harrington LE;Jope RS
通讯作者：
Jope RS
影响因子：
3.5
作者：
Alon, Lina Tsaadon;Pietrokovski, Shmuel;Eldar-Finkelman, Hagit
通讯作者：
Eldar-Finkelman, Hagit
影响因子：
2.5
作者：
Benedetti, F;Serretti, A;Smeraldi, B
通讯作者：
Smeraldi, B