Map4k4 Signaling Nodes in Metabolic and Cardiovascular Diseases.
Map4k4 Signaling Nodes in Metabolic and Cardiovascular Diseases.
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DOI：
10.1016/j.tem.2016.04.006
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发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Czech MP
中科院分区：
文献类型：
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作者：
Virbasius JV;Czech MP
Map4k4最初是在siRNA筛选中发现的，以组织特异性基因缺失为特征，目前正在成为葡萄糖稳态和心血管健康的调节因子。最近的研究表明，Map4k4基因消融或抑制其激酶活性可减轻胰岛素抵抗和动脉粥样硬化小鼠模型中的高血糖和斑块形成，并提示Map4k4在多种信号系统中发挥作用，包括NFκB激活、小GTPase调节、Hippo级联以及FERM结构域蛋白对细胞动力学的调节。这一新的有前途的研究领域提出了未来需要解决的关键问题，例如确定上述或其他效应物中哪一种介导Map4k4代谢和血管功能的控制，以及确定Map4k4的上游激活因子。
Map4k4, originally identified in siRNA screens and characterized by tissue specific gene deletions, is emerging as a regulator of glucose homeostasis and cardiovascular health. Recent studies have shown that Map4k4 gene ablation or inhibition of its kinase activity attenuates hyperglycemia and plaque formation in mouse models of insulin resistance and atherosclerosis, and suggest roles for Map4k4 in multiple signaling systems, including NFκB activation, small GTPase regulation, the Hippo cascade, and regulation of cell dynamics by FERM domain proteins. This new and promising area of inquiry raises key questions that need to be addressed in the future, such as defining which of the above or other effectors mediate Map4k4 control of metabolic and vascular functions, and identifying upstream activators of Map4k4.